Materiały źródłowe

• #1 Inborn Errors of Metabolism (IEM) – Inherited Metabolic Disorders

  https://my.clevelandclinic.org/health/diseases/17962-inherited-metabolic-disorders

  Inborn errors of metabolism, also known as inherited metabolic disorders or hereditary metabolic disorders, are a group of conditions that affect your ability to convert food into energy and remove waste and unhealthy substances from your body. […] A genetic mutation that happens when your cells divide and replicate during fetal development causes inborn errors of metabolism (IEM). […] Several possible genes cause each type of IEM. […] When you have an inborn error of metabolism, your enzymes dont have the instructions they need to do their job within your metabolism, which causes symptoms of the specific IEM that affects your body.

• #2 Inherited metabolic disorders – WikiLectures

  https://www.wikilectures.eu/w/Inherited_metabolic_disorders

  Inherited metabolic disorders (IMDs) form a diverse group of 700-800 diseases that are caused by enzyme deficiency, transport protein dysfunction or a disorder of another protein associated with a metabolic pathway. […] Insufficient production of the enzyme or the required protein occurs as a result of mutations in nuclear or mitochondrial DNA. […] The most common cause of inherited metabolic disorders are nuclear DNA mutations in germ cells (and thus in somatic cells) with typical monogenic Mendelian inheritance usually autosomal recessive, gonosomal recessive and dominant. A less common cause of IMD is mitochondrial DNA mutations, which are transmitted by the maternal type of inheritance. […] Mutations can be of the type of point mutations (missense, nonsense, synonymous mutations), deletions and insertions (with or without frameshift), and the degree of impairment of a given protein often cannot be directly determined from the type of mutation and its location. […] The affected protein is usually an enzyme of some metabolic pathway, which then binds to its product, which may be missing, and does not drain the substrate, which may accumulate, or metabolize to by-product.

• #3 Inherited Metabolic Disorders: Overview and Resources

  https://metab.ern-net.eu/inherited-metabolic-disorders/

  Inherited Metabolic Disorders (IMDs), in particular, represent a group of more than 1400 rare genetic pathologies, classified in 130 different biochemical groups, that impact both children and adults and are quite heterogeneous. […] Metabolic disorders are generally chronic and progressive and can involve multiple organs, thus early diagnosis and treatment are crucial to avoid further complications. […] IMDs are a complex class of conditions that can affect the metabolism of carbohydrates, amino acids, lipids, steroids but also nucleic acids, mitochondria and neurotransmitters. […] Disorders of intermediary metabolism involve pathways that mediate the breakdown of low-molecular weight nutrient compounds (such as proteins, carbohydrates, and lipids) or convert them into substrates for the biosynthesis of complex molecules.

• #4 Inherited metabolic disorders // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/inherited-metabolic-disorders

  Inherited metabolic disorders are medical conditions caused by changes in specific genes that affect metabolism. Different gene changes cause different types of inherited metabolic disorders. These gene changes are most commonly passed down from both parents. But sometimes the gene change comes only from one parent, most often from the mother. […] Inherited metabolic disorders are caused by changes in specific genes that affect metabolism. Different gene changes cause different types of inherited metabolic disorders. These gene changes are most commonly passed down from both parents. But sometimes the gene change comes only from one parent, most often from the mother. There are hundreds of inherited metabolic disorders caused by different genes.

• #5 Inherited metabolic disorders | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/inherited-metabolic-disorders?content_id=CON-20303979

  Caused by gene changes, these disorders affect the body’s ability to change food into energy. […] Inherited metabolic disorders are medical conditions caused by changes in specific genes that affect metabolism. Different gene changes cause different types of inherited metabolic disorders. […] Inherited metabolic disorders are caused by changes in specific genes that affect metabolism. Different gene changes cause different types of inherited metabolic disorders. These gene changes are most commonly passed down from both parents. But sometimes the gene change comes only from one parent, most often from the mother. There are hundreds of inherited metabolic disorders caused by different genes.

• #6 Inborn error of metabolism | Genetics, Causes & Treatment | Britannica

  https://www.britannica.com/science/inborn-error-of-metabolism

  inborn error of metabolism, any of multiple rare disorders that are caused by an inherited genetic defect and that alter the body’s ability to derive energy from nutrients. […] The metabolic diseases that result from inborn defects involve different aspects of human metabolism, including the handling of amino acids, lipids, carbohydrates, and nucleic acids. In most instances the underlying cause is the inheritance of a mutated enzyme, the normal function of which is the metabolic transformation of one metabolite into another, or of a mutated transport protein, the normal function of which is to assist in the movement of a compound across a cell membrane. […] Inheritance of inborn errors of metabolism usually conforms to an autosomal recessive pattern (two copies of the mutant gene, one from each parent, must be inherited to produce the signs and symptoms of disease). In some cases, however, inheritance may be dominant (only one copy of the mutated gene is needed) or sex-linked (the mutated gene is carried on a sex [X or Y] chromosome).

• #7 Inherited Metabolic Disorders: Types, Signs, Causes & Treatment

  https://www.webmd.com/a-to-z-guides/inherited-metabolic-disorder-types-and-treatments

  Inherited metabolic disorders are genetic conditions that result in metabolism problems. Most people with inherited metabolic disorders have a defective gene that results in lack of an enzyme. According to the latest count, 1,564 of these disorders have been identified. […] In most inherited metabolic disorders, a single enzyme is either not produced by the body at all or is produced in a form that doesnt work. The missing enzyme is like an absentee worker on the assembly line. Depending on that enzymes job, its absence means toxic chemicals may build up or an essential product may not be produced. […] The original cause of most genetic metabolic disorders is a gene mutation that occurred many generations ago. The gene mutation is passed along through the generations, ensuring its preservation.

• #8 Metabolic disorder: what is it, symptoms and treatment | Top Doctors

  https://www.topdoctors.co.uk/medical-dictionary/metabolic-disorder

  Metabolic disorders are commonly inherited from family where they have inherited a defective gene which results in enzyme deficiency. […] These are called inherited metabolic disorders. […] Most metabolic disorders are caused by the fact that a single enzyme is not made by the body or does not function properly. […] The code required to create that specific enzyme is contained on a pair of genes, which if defective can result in a metabolic disorder. […] However, only children that inherit two copies of a defective gene from their parents will develop a metabolic disorder. […] Inherited metabolic disorders cannot be prevented, however, if managed and treated early on, the prognosis is often better. […] There are no cures available for inherited metabolic disorders, however, treatment focuses on overcoming the problems with metabolism.

• #9 Overview of Hereditary Metabolic Disorders – Children’s Health Issues – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/children-s-health-issues/hereditary-metabolic-disorders/overview-of-hereditary-metabolic-disorders

  Hereditary metabolic disorders are inherited genetic conditions that cause problems in metabolic pathways and can result in organ damage. […] Hereditary metabolic disorders develop when children inherit defective genes that control metabolism. […] In most hereditary metabolic disorders, both parents of the affected child carry 1 copy of the abnormal gene. […] Some hereditary metabolic disorders are X-linked, which means only 1 copy of the abnormal gene can cause the disorder in boys. […] If a genetic abnormality affects the function of an enzyme or causes it to be deficient or missing altogether, various metabolic disorders can occur. […] These disorders usually result from one or both of the following: Inability to break down a substance that should be broken down, allowing a toxic intermediate substance to build up […] Inability to produce some essential substance.

• #10 Overview of Hereditary Metabolic Disorders – Children’s Health Issues – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/children-s-health-issues/hereditary-metabolic-disorders/overview-of-hereditary-metabolic-disorders

  Hereditary metabolic disorders are inherited genetic conditions that cause problems in metabolic pathways and can result in organ damage. […] Hereditary metabolic disorders develop when children inherit defective genes that control metabolism. […] In most hereditary metabolic disorders, both parents of the affected child carry 1 copy of the abnormal gene. […] Some hereditary metabolic disorders are X-linked, which means only 1 copy of the abnormal gene can cause the disorder in boys. […] If a genetic abnormality affects the function of an enzyme or causes it to be deficient or missing altogether, various metabolic disorders can occur. […] These disorders usually result from one or both of the following: Inability to break down a substance that should be broken down, allowing a toxic intermediate substance to build up […] Inability to produce some essential substance.

• #11 Overview of Hereditary Metabolic Disorders – Children’s Health Issues – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/children-s-health-issues/hereditary-metabolic-disorders/overview-of-hereditary-metabolic-disorders

  Hereditary metabolic disorders are inherited genetic conditions that cause problems in metabolic pathways and can result in organ damage. […] Hereditary metabolic disorders develop when children inherit defective genes that control metabolism. […] In most hereditary metabolic disorders, both parents of the affected child carry 1 copy of the abnormal gene. […] Some hereditary metabolic disorders are X-linked, which means only 1 copy of the abnormal gene can cause the disorder in boys. […] If a genetic abnormality affects the function of an enzyme or causes it to be deficient or missing altogether, various metabolic disorders can occur. […] These disorders usually result from one or both of the following: Inability to break down a substance that should be broken down, allowing a toxic intermediate substance to build up […] Inability to produce some essential substance.

• #12 Inborn Errors of Metabolism – Causes, Types, Symptoms, Diagnosis & Treatment

  https://www.medindia.net/health/conditions/inborn-errors-of-metabolism.htm

  Metabolism is a biochemical process by which our body converts nutrients from food to energy. Inborn errors of metabolism are a group of inherited congenital disorders in which the body cannot properly break down the nutrients from food. This results in the accumulation of food substrates in the cells of the body, leading to clinically significant consequences. […] A defect in a gene, also called mutation, that controls the production of a particular enzyme can result in a faulty enzyme or reduced quantity of the enzyme. The bodys metabolic pathway can thus be affected. […] Each gene has two copies and we inherit one copy from each parent. Mutations can arise in the individual for the first time or may be inherited from parents. The inheritance can occur in various patterns autosomal or sex-linked, dominant or recessive. Individuals who have an inherited metabolic disorder usually inherit the condition in an autosomal recessive pattern. […] Patterns of autosomal dominant inheritance, where only one defective gene is necessary to produce the condition, as well as sex-linked inheritance, where the defect is on the X or Y sex chromosome are also, though less commonly, associated with inborn errors or metabolism.

• #13 Inherited metabolic disorders – WikiLectures

  https://www.wikilectures.eu/w/Inherited_metabolic_disorders

  Inherited metabolic disorders (IMDs) form a diverse group of 700-800 diseases that are caused by enzyme deficiency, transport protein dysfunction or a disorder of another protein associated with a metabolic pathway. […] Insufficient production of the enzyme or the required protein occurs as a result of mutations in nuclear or mitochondrial DNA. […] The most common cause of inherited metabolic disorders are nuclear DNA mutations in germ cells (and thus in somatic cells) with typical monogenic Mendelian inheritance usually autosomal recessive, gonosomal recessive and dominant. A less common cause of IMD is mitochondrial DNA mutations, which are transmitted by the maternal type of inheritance. […] Mutations can be of the type of point mutations (missense, nonsense, synonymous mutations), deletions and insertions (with or without frameshift), and the degree of impairment of a given protein often cannot be directly determined from the type of mutation and its location. […] The affected protein is usually an enzyme of some metabolic pathway, which then binds to its product, which may be missing, and does not drain the substrate, which may accumulate, or metabolize to by-product.

• #14 Inherited metabolic disorders – WikiLectures

  https://www.wikilectures.eu/w/Inherited_metabolic_disorders

  Inherited metabolic disorders (IMDs) form a diverse group of 700-800 diseases that are caused by enzyme deficiency, transport protein dysfunction or a disorder of another protein associated with a metabolic pathway. […] Insufficient production of the enzyme or the required protein occurs as a result of mutations in nuclear or mitochondrial DNA. […] The most common cause of inherited metabolic disorders are nuclear DNA mutations in germ cells (and thus in somatic cells) with typical monogenic Mendelian inheritance usually autosomal recessive, gonosomal recessive and dominant. A less common cause of IMD is mitochondrial DNA mutations, which are transmitted by the maternal type of inheritance. […] Mutations can be of the type of point mutations (missense, nonsense, synonymous mutations), deletions and insertions (with or without frameshift), and the degree of impairment of a given protein often cannot be directly determined from the type of mutation and its location. […] The affected protein is usually an enzyme of some metabolic pathway, which then binds to its product, which may be missing, and does not drain the substrate, which may accumulate, or metabolize to by-product.

• #15 Inherited metabolic disorders – WikiLectures

  https://www.wikilectures.eu/w/Inherited_metabolic_disorders

  Inherited metabolic disorders (IMDs) form a diverse group of 700-800 diseases that are caused by enzyme deficiency, transport protein dysfunction or a disorder of another protein associated with a metabolic pathway. […] Insufficient production of the enzyme or the required protein occurs as a result of mutations in nuclear or mitochondrial DNA. […] The most common cause of inherited metabolic disorders are nuclear DNA mutations in germ cells (and thus in somatic cells) with typical monogenic Mendelian inheritance usually autosomal recessive, gonosomal recessive and dominant. A less common cause of IMD is mitochondrial DNA mutations, which are transmitted by the maternal type of inheritance. […] Mutations can be of the type of point mutations (missense, nonsense, synonymous mutations), deletions and insertions (with or without frameshift), and the degree of impairment of a given protein often cannot be directly determined from the type of mutation and its location. […] The affected protein is usually an enzyme of some metabolic pathway, which then binds to its product, which may be missing, and does not drain the substrate, which may accumulate, or metabolize to by-product.

• #16 Cause of rare genetic metabolic disorder | ScienceDaily

  https://www.sciencedaily.com/releases/2019/04/190415172153.htm

  A new study is the first to identify a rarely-seen type of DNA mutation as the cause of an inherited metabolic disorder. […] Inherited metabolic disorders — where the body can’t break down specific nutrients from food leading to a range of serious health problems — are often caused by a defective gene. […] To date, DNA repeat expansions have been linked to approximately 30 different diseases. […] „For kids with rare diseases and their families, finding the root causes of their disorders is tremendously important,” said Dr. Wyeth Wasserman, a co-author of the study. […] The gene identified as the cause of this particular disorder is an enzyme that enables the body to turn an amino acid called glutamine into glutamate. […] More work is needed to determine how exactly this genetic error leads to disease, but it’s likely that either a build-up of glutamine or the lack of glutamate caused the children’s serious developmental delays and disabilities including difficulty with language, speech, balance and coordination. […] „We can do better for children with rare diseases. For the 50 per cent who can’t find answers, this discovery and new approach will help us dig in and potentially find the causes of their disease,” said Richmond.

• #17 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20190416/Researchers-identify-cause-of-inherited-metabolic-disorder.aspx

  A new study from BC Children’s Hospital, the University of British Columbia (UBC) and an international team of researchers published in the New England Journal of Medicine is the first to identify a rarely-seen type of DNA mutation as the cause of an inherited metabolic disorder. […] Inherited metabolic disorders — where the body can’t break down specific nutrients from food leading to a range of serious health problems — are often caused by a defective gene. […] In this important study, researchers found an unusual genetic mutation behind three children’s undiagnosed, degenerative conditions: a repeat expansion of DNA. […] The gene identified as the cause of this particular disorder is an enzyme that enables the body to turn an amino acid called glutamine into glutamate. […] More work is needed to determine how exactly this genetic error leads to disease, but it’s likely that either a build-up of glutamine or the lack of glutamate caused the children’s serious developmental delays and disabilities including difficulty with language, speech, balance and coordination.

• #18 Inherited metabolic disorders – WikiLectures

  https://www.wikilectures.eu/w/Inherited_metabolic_disorders

  Inherited metabolic disorders (IMDs) form a diverse group of 700-800 diseases that are caused by enzyme deficiency, transport protein dysfunction or a disorder of another protein associated with a metabolic pathway. […] Insufficient production of the enzyme or the required protein occurs as a result of mutations in nuclear or mitochondrial DNA. […] The most common cause of inherited metabolic disorders are nuclear DNA mutations in germ cells (and thus in somatic cells) with typical monogenic Mendelian inheritance usually autosomal recessive, gonosomal recessive and dominant. A less common cause of IMD is mitochondrial DNA mutations, which are transmitted by the maternal type of inheritance. […] Mutations can be of the type of point mutations (missense, nonsense, synonymous mutations), deletions and insertions (with or without frameshift), and the degree of impairment of a given protein often cannot be directly determined from the type of mutation and its location. […] The affected protein is usually an enzyme of some metabolic pathway, which then binds to its product, which may be missing, and does not drain the substrate, which may accumulate, or metabolize to by-product.

• #19 Inborn Errors of Metabolism: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/804757-overview

  Inborn errors of metabolism describes a class of over 1000 inherited disorders caused by mutations in genes coding for proteins that function in metabolism. Most of the disorders are inherited as autosomal recessive, but some are autosomal dominant or X-linked. […] IEMs were initially thought to be caused by a specific single-gene mutation, but genetic characterization of variation in clinical manifestations led to the understanding that IEMs can be caused by different gene mutations that result in the same or similar diagnostic biochemical abnormalities. […] The presentation of specific IEMs as a spectrum of disease phenotypes in which a clear correlation between the severity of mutation at the affected locus and the phenotype (genotype-phenotype correlation) is often lacking and impacts the ability to predict disease course. […] Additional genes and environmental, epigenetic, and microbiome factors are also potential modifying etiologic factors in individual IEMs.

• #20 Overview of Hereditary Metabolic Disorders – Children’s Health Issues – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/children-s-health-issues/hereditary-metabolic-disorders/overview-of-hereditary-metabolic-disorders

  Hereditary metabolic disorders are inherited genetic conditions that cause problems in metabolic pathways and can result in organ damage. […] Hereditary metabolic disorders develop when children inherit defective genes that control metabolism. […] In most hereditary metabolic disorders, both parents of the affected child carry 1 copy of the abnormal gene. […] Some hereditary metabolic disorders are X-linked, which means only 1 copy of the abnormal gene can cause the disorder in boys. […] If a genetic abnormality affects the function of an enzyme or causes it to be deficient or missing altogether, various metabolic disorders can occur. […] These disorders usually result from one or both of the following: Inability to break down a substance that should be broken down, allowing a toxic intermediate substance to build up […] Inability to produce some essential substance.

• #21 Inborn error of metabolism | Genetics, Causes & Treatment | Britannica

  https://www.britannica.com/science/inborn-error-of-metabolism

  inborn error of metabolism, any of multiple rare disorders that are caused by an inherited genetic defect and that alter the body’s ability to derive energy from nutrients. […] The metabolic diseases that result from inborn defects involve different aspects of human metabolism, including the handling of amino acids, lipids, carbohydrates, and nucleic acids. In most instances the underlying cause is the inheritance of a mutated enzyme, the normal function of which is the metabolic transformation of one metabolite into another, or of a mutated transport protein, the normal function of which is to assist in the movement of a compound across a cell membrane. […] Inheritance of inborn errors of metabolism usually conforms to an autosomal recessive pattern (two copies of the mutant gene, one from each parent, must be inherited to produce the signs and symptoms of disease). In some cases, however, inheritance may be dominant (only one copy of the mutated gene is needed) or sex-linked (the mutated gene is carried on a sex [X or Y] chromosome).

• #22 Inherited metabolic diseases | Basicmedical Key

  https://basicmedicalkey.com/inherited-metabolic-diseases/

  Many inherited diseases are known to be due to the genetically determined absence or modification of specific proteins. […] However, in the majority of such diseases, the protein in question is an enzyme, and the effect is to cause a metabolic disorder. […] Whatever the cause, the clinical features of inherited metabolic diseases stem directly from the metabolic abnormalities to which they give rise. […] In recent years, application of the techniques of molecular genetic analysis has massively increased our understanding of these conditions. […] It is now clear that many inherited metabolic diseases can arise because of one of a number of genetic defects. […] Most inherited metabolic diseases show autosomal recessive inheritance; heterozygotes are usually phenotypically normal although they are carriers of the condition.

• #23 Inborn error of metabolism | Genetics, Causes & Treatment | Britannica

  https://www.britannica.com/science/inborn-error-of-metabolism

  inborn error of metabolism, any of multiple rare disorders that are caused by an inherited genetic defect and that alter the body’s ability to derive energy from nutrients. […] The metabolic diseases that result from inborn defects involve different aspects of human metabolism, including the handling of amino acids, lipids, carbohydrates, and nucleic acids. In most instances the underlying cause is the inheritance of a mutated enzyme, the normal function of which is the metabolic transformation of one metabolite into another, or of a mutated transport protein, the normal function of which is to assist in the movement of a compound across a cell membrane. […] Inheritance of inborn errors of metabolism usually conforms to an autosomal recessive pattern (two copies of the mutant gene, one from each parent, must be inherited to produce the signs and symptoms of disease). In some cases, however, inheritance may be dominant (only one copy of the mutated gene is needed) or sex-linked (the mutated gene is carried on a sex [X or Y] chromosome).

• #24 Inborn Errors of Metabolism – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459183/

  Inborn errors of metabolism are inherited disorders caused by mutations in genes coding for proteins that function in metabolism. Most are inherited as autosomal recessive. Rarely, they are autosomal dominant and X-linked. Environmental, epigenetic, and microbiome factors and additional genes are potential modifying etiologic factors in those with inborn errors of metabolism. […] Inborn errors of metabolism are a heterogeneous group of disorders that may be inherited or may occur as the result of spontaneous mutations. These diseases involve failure of the metabolic pathways involved in either the break-down or storage of carbohydrates, fatty acids, and proteins.

• #25 Overview of Hereditary Metabolic Disorders – Children’s Health Issues – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/children-s-health-issues/hereditary-metabolic-disorders/overview-of-hereditary-metabolic-disorders

  Hereditary metabolic disorders are inherited genetic conditions that cause problems in metabolic pathways and can result in organ damage. […] Hereditary metabolic disorders develop when children inherit defective genes that control metabolism. […] In most hereditary metabolic disorders, both parents of the affected child carry 1 copy of the abnormal gene. […] Some hereditary metabolic disorders are X-linked, which means only 1 copy of the abnormal gene can cause the disorder in boys. […] If a genetic abnormality affects the function of an enzyme or causes it to be deficient or missing altogether, various metabolic disorders can occur. […] These disorders usually result from one or both of the following: Inability to break down a substance that should be broken down, allowing a toxic intermediate substance to build up […] Inability to produce some essential substance.

• #26 Causes/Inheritance – Metabolic Myopathies – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/metabolic-myopathies/causes-inheritance

  In metabolic myopathies, missing enzymes prevent mitochondria from properly processing fuel, and no energy is produced for muscle function. The metabolic diseases of muscle are caused by genetic defects that interfere with chemical reactions involved in drawing energy from food. […] Nine of the metabolic diseases discussed on this website are caused by defects in the enzymes that control chemical reactions used to break down food. […] Most of the metabolic diseases of muscle are inherited in an autosomal recessive pattern, meaning that a person needs two defective genes in order to have the disease. […] Thus, the disease appears to have occurred out of the blue, but in reality, both parents may be carriers, silently harboring the genetic mutation (a flaw in the gene). […] Other metabolic disorders, such as phosphoglycerate kinase deficiency, are inherited in an X-linked recessive pattern, meaning the disease usually only affects males, although females are carriers. […] Finally, metabolic disorders actually can occur out of the blue when a new mutation appears with a baby’s conception. These are called spontaneous mutations, and after they occur, they can be passed on to the next generation.

• #27 Inherited metabolic disorders – WikiLectures

  https://www.wikilectures.eu/w/Inherited_metabolic_disorders

  Inherited metabolic disorders (IMDs) form a diverse group of 700-800 diseases that are caused by enzyme deficiency, transport protein dysfunction or a disorder of another protein associated with a metabolic pathway. […] Insufficient production of the enzyme or the required protein occurs as a result of mutations in nuclear or mitochondrial DNA. […] The most common cause of inherited metabolic disorders are nuclear DNA mutations in germ cells (and thus in somatic cells) with typical monogenic Mendelian inheritance usually autosomal recessive, gonosomal recessive and dominant. A less common cause of IMD is mitochondrial DNA mutations, which are transmitted by the maternal type of inheritance. […] Mutations can be of the type of point mutations (missense, nonsense, synonymous mutations), deletions and insertions (with or without frameshift), and the degree of impairment of a given protein often cannot be directly determined from the type of mutation and its location. […] The affected protein is usually an enzyme of some metabolic pathway, which then binds to its product, which may be missing, and does not drain the substrate, which may accumulate, or metabolize to by-product.

• #28 Inherited metabolic disorders // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/inherited-metabolic-disorders

  Inherited metabolic disorders are medical conditions caused by changes in specific genes that affect metabolism. Different gene changes cause different types of inherited metabolic disorders. These gene changes are most commonly passed down from both parents. But sometimes the gene change comes only from one parent, most often from the mother. […] Inherited metabolic disorders are caused by changes in specific genes that affect metabolism. Different gene changes cause different types of inherited metabolic disorders. These gene changes are most commonly passed down from both parents. But sometimes the gene change comes only from one parent, most often from the mother. There are hundreds of inherited metabolic disorders caused by different genes.

• #29 Causes/Inheritance – Metabolic Myopathies – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/metabolic-myopathies/causes-inheritance

  In metabolic myopathies, missing enzymes prevent mitochondria from properly processing fuel, and no energy is produced for muscle function. The metabolic diseases of muscle are caused by genetic defects that interfere with chemical reactions involved in drawing energy from food. […] Nine of the metabolic diseases discussed on this website are caused by defects in the enzymes that control chemical reactions used to break down food. […] Most of the metabolic diseases of muscle are inherited in an autosomal recessive pattern, meaning that a person needs two defective genes in order to have the disease. […] Thus, the disease appears to have occurred out of the blue, but in reality, both parents may be carriers, silently harboring the genetic mutation (a flaw in the gene). […] Other metabolic disorders, such as phosphoglycerate kinase deficiency, are inherited in an X-linked recessive pattern, meaning the disease usually only affects males, although females are carriers. […] Finally, metabolic disorders actually can occur out of the blue when a new mutation appears with a baby’s conception. These are called spontaneous mutations, and after they occur, they can be passed on to the next generation.

• #30 Inherited metabolic diseases | Basicmedical Key

  https://basicmedicalkey.com/inherited-metabolic-diseases/

  Because they are individually rare, it is important for the clinician to have a high index of suspicion and actively consider the possibility that an illness may be caused by an inherited metabolic disease. […] The techniques of molecular genetic analysis are now also being increasingly used in the screening and diagnosis of inherited metabolic diseases. […] Glucose 6-phosphatase deficiency exemplifies the development of a clinical syndrome due to lack of formation of the product of an enzyme-catalysed reaction. […] Glucose 6-phosphatase deficiency also exemplifies the consequences of accumulation of a precursor other than the immediate substrate of the defective enzyme. […] Three enzyme defects can cause galactosaemia, and exemplify the production of a clinical syndrome due to the accumulation of a substrate of the missing enzyme. […] Phenylketonuria (PKU) is another condition in which the accumulation of the substrate of the missing enzyme gives rise to a clinical syndrome. […] The enzyme concerned is phenylalanine hydroxylase, which hydroxylates phenylalanine to form tyrosine.

• #31 Metabolic disease | Definition, Origins, Types, & Facts | Britannica

  https://www.britannica.com/science/metabolic-disease

  If an enzyme is missing or has diminished activity, the pathway becomes blocked, and the formation of the final product is deficient, resulting in disease. […] Low activity of an enzyme may result in the subsequent accumulation of the enzyme’s substrate, which may be toxic at high levels. […] The consequences of metabolic imbalance may be severe; intellectual disability, seizures, decreased muscle tone, organ failure, blindness, and deafness may occur, depending on which enzyme is dysfunctional.

• #32 Inherited metabolic diseases | Basicmedical Key

  https://basicmedicalkey.com/inherited-metabolic-diseases/

  Because they are individually rare, it is important for the clinician to have a high index of suspicion and actively consider the possibility that an illness may be caused by an inherited metabolic disease. […] The techniques of molecular genetic analysis are now also being increasingly used in the screening and diagnosis of inherited metabolic diseases. […] Glucose 6-phosphatase deficiency exemplifies the development of a clinical syndrome due to lack of formation of the product of an enzyme-catalysed reaction. […] Glucose 6-phosphatase deficiency also exemplifies the consequences of accumulation of a precursor other than the immediate substrate of the defective enzyme. […] Three enzyme defects can cause galactosaemia, and exemplify the production of a clinical syndrome due to the accumulation of a substrate of the missing enzyme. […] Phenylketonuria (PKU) is another condition in which the accumulation of the substrate of the missing enzyme gives rise to a clinical syndrome. […] The enzyme concerned is phenylalanine hydroxylase, which hydroxylates phenylalanine to form tyrosine.

• #33 Inherited metabolic disorders involving the eye: a clinico-biochemical perspective | Eye

  https://www.nature.com/articles/eye2009229

  The mechanisms by which systemic metabolic disease contributes to ocular defects remains to be elucidated. The various mechanisms involved could be due to direct toxic mechanisms of abnormal metabolic products, accumulation of normal metabolites by errors of synthetic pathways, or by deficient energy metabolism. […] Every metabolic disease has several forms that vary in age of onset, clinical severity, and often, mode of inheritance. Environmental factors may trigger the onset and severity of disease. […] Recognition of IMDs is important as it is quite common in incidence. […] The indications for metabolic studies to rule out the possibility of IMDs are discussed in Table 2. Early diagnosis is important, as in most cases, dietary restriction and early therapy prevents onset of disability.

• #34 Inherited metabolic disorders involving the eye: a clinico-biochemical perspective | Eye

  https://www.nature.com/articles/eye2009229

  The mechanisms by which systemic metabolic disease contributes to ocular defects remains to be elucidated. The various mechanisms involved could be due to direct toxic mechanisms of abnormal metabolic products, accumulation of normal metabolites by errors of synthetic pathways, or by deficient energy metabolism. […] Every metabolic disease has several forms that vary in age of onset, clinical severity, and often, mode of inheritance. Environmental factors may trigger the onset and severity of disease. […] Recognition of IMDs is important as it is quite common in incidence. […] The indications for metabolic studies to rule out the possibility of IMDs are discussed in Table 2. Early diagnosis is important, as in most cases, dietary restriction and early therapy prevents onset of disability.

• #35 Inherited metabolic diseases | Basicmedical Key

  https://basicmedicalkey.com/inherited-metabolic-diseases/

  Because they are individually rare, it is important for the clinician to have a high index of suspicion and actively consider the possibility that an illness may be caused by an inherited metabolic disease. […] The techniques of molecular genetic analysis are now also being increasingly used in the screening and diagnosis of inherited metabolic diseases. […] Glucose 6-phosphatase deficiency exemplifies the development of a clinical syndrome due to lack of formation of the product of an enzyme-catalysed reaction. […] Glucose 6-phosphatase deficiency also exemplifies the consequences of accumulation of a precursor other than the immediate substrate of the defective enzyme. […] Three enzyme defects can cause galactosaemia, and exemplify the production of a clinical syndrome due to the accumulation of a substrate of the missing enzyme. […] Phenylketonuria (PKU) is another condition in which the accumulation of the substrate of the missing enzyme gives rise to a clinical syndrome. […] The enzyme concerned is phenylalanine hydroxylase, which hydroxylates phenylalanine to form tyrosine.

• #36 Inherited Metabolic Disorders | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/pediatrics/cancer-care/types/pediatric-blood-disorders/about-pediatric-blood-disorders/inherited-metabolic-disorders

  An inherited blood disorder is what we often know as something that runs in the family. It is passed down from one or both parents to a child. […] Inborn errors of metabolism are a diverse group of disorders caused by an inherited deficiency or defect in a single enzyme or protein. Your body needs these vital enzymes and proteins. When there are not enough of them, the body cannot break down certain large molecules correctly. As a result, a harmful amount of these large molecules, or storage materials, builds up and damages organs and body systems. […] The MSK Kids team works together to diagnose these disorders and start treatment as early as possible. Children with these inborn errors of metabolism have access to our expertise in stem cell transplantation, the only effective therapy. They may also be able to participate in a clinical trial of novel gene therapies. The decision to enroll in a clinical trial is entirely voluntary.

• #37 Metabolic Disorders | Kennedy Krieger Institute

  https://www.kennedykrieger.org/patient-care/conditions/metabolic-disorders

  Genetic metabolic diseases are congenital errors of the body’s chemistry that affect the way in which food is assimilated, energy generated and tissue growth enabled. […] Most metabolic disorders are caused by the genetic deficiency of an enzyme that is needed to convert one chemical into another. […] The deficiency of phenylalanine hydroxylase leads to the accumulation of a toxic level of phenylalanine and a deficiency of tyrosine, both of which damage the developing brain and cause severe intellectual disabilities. […] Other adverse effects of metabolic diseases include seizures, movement disorders, poor growth, muscle weakness, fasting intolerance and disproportionate illness with simple childhood infections or immunizations. […] Some metabolic diseases become manifest in the first few days of life, whereas others require a stress, such as a fever or fasting during an illness, to become manifest. […] Although each metabolic disease individually is rare, there are more than 1,300 known metabolic diseases, and collectively they represent a significant cause of illness and disability in children.

• #38 Metabolic disorders

  https://bwc.nhs.uk/metabolic-disorders/

  female doctor Within the Inherited Metabolic Disease (IMD) team, we deal with many different types of conditions ranging from deficiencies in enzymes to the body unable to use certain nutrients. […] Phenylketonuria (PKU) – an inherited condition caused by a deficiency in the enzyme phenylalanine hydroxylase which can cause learning and physical disabilities if left untreated. […] Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) – a condition where the body is unable to fully use fat as an energy supply. […] Maple syrup urine disease (MSUD) – a condition where the body loses the ability to use three of the essential amino acids in protein. […] Glycogen storage disease (GSD) – a group of conditions where the liver and/or muscles can’t release glucose properly from stored glycogen.

• #39 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Pancreatitis can be a complication in citrin deficiency, maple syrup urine disease (types 1a, 1b, and 2), isovaleric acidemia, hydroxymethylglutaric aciduria, propionic acidemia, methylmalonic aciduria, and -ketothiolase deficiency, disorders in which acidosis, ketosis, vomiting, and abdominal pain are common during crises of metabolic decompensation. […] Symptoms of biotinidase deficiency derive from the patients inability to reutilize biotin. […] Feeding difficulties, vomiting, diarrhea, glossitis, and stomatitis may be seen. […] The most common types of inborn errors of carbohydrate metabolism are glycogen storage diseases (GSD) and inborn errors of galactose and fructose metabolism. […] Patients with GSD with liver involvement present in infancy with a tendency toward hypoglycemia, which can be severe in fasting, and marked hepatomegaly.

• #40 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Pancreatitis can be a complication in citrin deficiency, maple syrup urine disease (types 1a, 1b, and 2), isovaleric acidemia, hydroxymethylglutaric aciduria, propionic acidemia, methylmalonic aciduria, and -ketothiolase deficiency, disorders in which acidosis, ketosis, vomiting, and abdominal pain are common during crises of metabolic decompensation. […] Symptoms of biotinidase deficiency derive from the patients inability to reutilize biotin. […] Feeding difficulties, vomiting, diarrhea, glossitis, and stomatitis may be seen. […] The most common types of inborn errors of carbohydrate metabolism are glycogen storage diseases (GSD) and inborn errors of galactose and fructose metabolism. […] Patients with GSD with liver involvement present in infancy with a tendency toward hypoglycemia, which can be severe in fasting, and marked hepatomegaly.

• #41 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Pancreatitis can be a complication in citrin deficiency, maple syrup urine disease (types 1a, 1b, and 2), isovaleric acidemia, hydroxymethylglutaric aciduria, propionic acidemia, methylmalonic aciduria, and -ketothiolase deficiency, disorders in which acidosis, ketosis, vomiting, and abdominal pain are common during crises of metabolic decompensation. […] Symptoms of biotinidase deficiency derive from the patients inability to reutilize biotin. […] Feeding difficulties, vomiting, diarrhea, glossitis, and stomatitis may be seen. […] The most common types of inborn errors of carbohydrate metabolism are glycogen storage diseases (GSD) and inborn errors of galactose and fructose metabolism. […] Patients with GSD with liver involvement present in infancy with a tendency toward hypoglycemia, which can be severe in fasting, and marked hepatomegaly.

• #42 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Symptoms are due to the inability to release glucose from the liver and severely impaired glycogenolysis and glucogenesis. […] Disorders of insulin secretion and signaling have pancreatic symptoms varying from hypoplasia in Beckwith-Wiedemann syndrome to endocrine pancreatic dysfunction in RFX6 deficiency. […] Primary mitochondrial disorders (PMD) represent a group of defects of mitochondrial biogenesis or function, caused by inherited or sporadic variants in mitochondrial DNA (mtDNA) or in nuclear-encoded genes necessary for mitochondrial function. […] GI symptoms are a relatively common yet often overlooked feature of many primary mitochondrial disorders, affecting approximately 15% of patients with MtDNA disease. […] Although GI manifestations are not the primary feature of most MIDs, gut dysmotility predominates the clinical presentation in most cases of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

• #43 Inherited metabolic diseases | Basicmedical Key

  https://basicmedicalkey.com/inherited-metabolic-diseases/

  Because they are individually rare, it is important for the clinician to have a high index of suspicion and actively consider the possibility that an illness may be caused by an inherited metabolic disease. […] The techniques of molecular genetic analysis are now also being increasingly used in the screening and diagnosis of inherited metabolic diseases. […] Glucose 6-phosphatase deficiency exemplifies the development of a clinical syndrome due to lack of formation of the product of an enzyme-catalysed reaction. […] Glucose 6-phosphatase deficiency also exemplifies the consequences of accumulation of a precursor other than the immediate substrate of the defective enzyme. […] Three enzyme defects can cause galactosaemia, and exemplify the production of a clinical syndrome due to the accumulation of a substrate of the missing enzyme. […] Phenylketonuria (PKU) is another condition in which the accumulation of the substrate of the missing enzyme gives rise to a clinical syndrome. […] The enzyme concerned is phenylalanine hydroxylase, which hydroxylates phenylalanine to form tyrosine.

• #44 Metabolic disorders

  https://bwc.nhs.uk/metabolic-disorders/

  Galactosaemia – a rare genetic metabolic disorder affecting the body’s ability to metabolise the milk sugar, galactose properly. […] Urea cycle defects – genetic disorders caused by a deficiency of one of the enzymes in the urea cycle, responsible for removing ammonia from the bloodstream. […] Familial hypercholesterolaemia (FH) – a condition where there are abnormally high levels of cholesterol in the blood. […] Congenital disorders of glycosylation (CDG) – a group of rare metabolic diseases caused by defects in how sugar side chains are added to proteins. […] Lysosomal storage disorders (LSD) – enzyme deficiencies in the breakdown of complex molecules. […] Organic acidemias – a group of metabolic disorders which disrupts the normal amino acid metabolism, particularly branched-chain amino acids causing a buildup of acids which are usually not present. […] Mitochondrial disorders – a group of disorders in which the ability of the body to generate energy is impaired.

• #45 Inherited metabolic diseases | Basicmedical Key

  https://basicmedicalkey.com/inherited-metabolic-diseases/

  Because they are individually rare, it is important for the clinician to have a high index of suspicion and actively consider the possibility that an illness may be caused by an inherited metabolic disease. […] The techniques of molecular genetic analysis are now also being increasingly used in the screening and diagnosis of inherited metabolic diseases. […] Glucose 6-phosphatase deficiency exemplifies the development of a clinical syndrome due to lack of formation of the product of an enzyme-catalysed reaction. […] Glucose 6-phosphatase deficiency also exemplifies the consequences of accumulation of a precursor other than the immediate substrate of the defective enzyme. […] Three enzyme defects can cause galactosaemia, and exemplify the production of a clinical syndrome due to the accumulation of a substrate of the missing enzyme. […] Phenylketonuria (PKU) is another condition in which the accumulation of the substrate of the missing enzyme gives rise to a clinical syndrome. […] The enzyme concerned is phenylalanine hydroxylase, which hydroxylates phenylalanine to form tyrosine.

• #46 Biochemical Genetics – Seattle Children’s

  https://www.seattlechildrens.org/clinics/genetics/biochemical-genetics/

  Inherited conditions that disrupt how the body makes or uses proteins, fats or carbohydrates are called biochemical genetic disorders. Other names for these are inherited metabolic disorders or inborn errors of metabolism. […] In children with inherited metabolic disorders, 1 or more changes in a gene lead to a problem with 1 of these chemical reactions. This can cause symptoms that range from mild to life-threatening. […] There are hundreds of genetic disorders related to metabolism. We treat these and many others. […] Children with these disorders cannot use fats for energy. This can lead to low blood sugar, muscle weakness and heart problems. […] Many building blocks of the body, such as proteins, fats and other molecules, need to have sugars attached to them to work correctly. […] Problems with how a child’s body breaks down or uses carbohydrates can cause a harmful amount of carbohydrate to build up in their body. This can lead to health problems.

• #47 Metabolic disorders

  https://bwc.nhs.uk/metabolic-disorders/

  female doctor Within the Inherited Metabolic Disease (IMD) team, we deal with many different types of conditions ranging from deficiencies in enzymes to the body unable to use certain nutrients. […] Phenylketonuria (PKU) – an inherited condition caused by a deficiency in the enzyme phenylalanine hydroxylase which can cause learning and physical disabilities if left untreated. […] Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) – a condition where the body is unable to fully use fat as an energy supply. […] Maple syrup urine disease (MSUD) – a condition where the body loses the ability to use three of the essential amino acids in protein. […] Glycogen storage disease (GSD) – a group of conditions where the liver and/or muscles can’t release glucose properly from stored glycogen.

• #48 The Reciprocal Interplay between Infections and Inherited Metabolic Disorders

  https://www.mdpi.com/2076-2607/11/10/2545

  For these reasons, metabolic disorders of energy production potentially function as immunopathies predisposing to different kinds of infections. […] However, the link between infections and IMDs may involve other pathogenetic mechanisms of different cellular pathways, with infective agents functioning as effect or cause of the metabolic derangement. […] Infections are a well-known trigger for FAOD metabolic decompensation. […] Infections can also worsen the clinical course of IMDs not subjected to AMD, provoking chronic disruption of metabolic parameters and an unsatisfactory clinical outcome. […] The data reviewed here strongly suggest that the role of infections in many types of IMDs deserves greater attention for a better management of these disorders and a more focused therapeutic approach.

• #49 The Reciprocal Interplay between Infections and Inherited Metabolic Disorders

  https://www.mdpi.com/2076-2607/11/10/2545

  Infections represent the main cause of acute metabolic derangements and/or the worsening of the clinical course of many inherited metabolic disorders (IMDs). […] Classically, infections have been considered as the consequence of a compromised immune system due to a biochemical defect of energy production. […] An adjunctive pathogenetic mechanism is related to a genetically altered protein-attached glycans composition, due to congenital glycosilation defects. […] Intercurrent infections are the most common trigger of acute metabolic decompensation (AMD) due to the increased metabolic demand during infection, leading to a catabolic state. […] The reason behind this close relationship can be, first of all, attributed to the fact that infections represent a stimulus to the functioning of the immune system, which is a large user of energy, whose production and recycling is essential for its correct functioning.

• #50 Metabolic disorders

  https://bwc.nhs.uk/metabolic-disorders/

  Galactosaemia – a rare genetic metabolic disorder affecting the body’s ability to metabolise the milk sugar, galactose properly. […] Urea cycle defects – genetic disorders caused by a deficiency of one of the enzymes in the urea cycle, responsible for removing ammonia from the bloodstream. […] Familial hypercholesterolaemia (FH) – a condition where there are abnormally high levels of cholesterol in the blood. […] Congenital disorders of glycosylation (CDG) – a group of rare metabolic diseases caused by defects in how sugar side chains are added to proteins. […] Lysosomal storage disorders (LSD) – enzyme deficiencies in the breakdown of complex molecules. […] Organic acidemias – a group of metabolic disorders which disrupts the normal amino acid metabolism, particularly branched-chain amino acids causing a buildup of acids which are usually not present. […] Mitochondrial disorders – a group of disorders in which the ability of the body to generate energy is impaired.

• #51 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  We have identified 339 IMDs associated with various types of GI involvement which we classified into seven groups according to the lesion site of the GI system. […] Feeding difficulties represent the most common abnormality reported for IMDs with GI involvement (127/339; 37%) followed by intestinal problems (103/339; 30%), vomiting (75/339; 22%), stomach and pancreas involvement (28/339; 8% each), and esophagus involvement (15/339; 4%). […] Failure to thrive is common among individuals with an IMD involving nitrogen-containing compounds. […] Vomiting and feeding difficulties are also commonly observed, as many affected individuals cannot tolerate protein ingestion and must follow a protein restricted diet. […] Chronic vomiting is a characteristic feature among branched-chain organic acidurias and urea cycle disorders in which hyperammonemia occurs.

• #52 Metabolic and genetic disorders mimicking cerebral palsy | Neurosciences Journal

  https://nsj.org.sa/content/24/3/155

  Biotinidase deficiency is an autosomal recessive inherited form of multiple carboxylase deficiency. […] Arginase deficiency is an autosomal recessive urea cycle disorder. […] Aicardi-Goutires syndrome is a genetically inherited autoimmune-mediated encephalopathy. […] Dyskinesia is defined as abnormal involuntary movements, with fluctuating patterns of tone and posture. […] GCH1-related dopa-responsive dystonia is commonly misdiagnosed as CP. […] Sepiapterin reductase deficiency is an autosomal recessive disorder caused by mutation in the sepiapterin reductase gene. […] Glutaric aciduria type 1 is a rare autosomal recessive metabolic disorder caused by alteration in the glutaryl-CoA dehydrogenase gene (GCDH). […] Cerebral creatine deficiency syndromes are a group of the creatine synthesis and transport with 3 recognized syndromes: guanidinoacetate methyltransferase (GAMT), arginine glycine amidinotransferase (AGAT), and X-linked creatine transporter deficiency (SLC6A8).

• #53 Metabolic disorders

  https://bwc.nhs.uk/metabolic-disorders/

  Galactosaemia – a rare genetic metabolic disorder affecting the body’s ability to metabolise the milk sugar, galactose properly. […] Urea cycle defects – genetic disorders caused by a deficiency of one of the enzymes in the urea cycle, responsible for removing ammonia from the bloodstream. […] Familial hypercholesterolaemia (FH) – a condition where there are abnormally high levels of cholesterol in the blood. […] Congenital disorders of glycosylation (CDG) – a group of rare metabolic diseases caused by defects in how sugar side chains are added to proteins. […] Lysosomal storage disorders (LSD) – enzyme deficiencies in the breakdown of complex molecules. […] Organic acidemias – a group of metabolic disorders which disrupts the normal amino acid metabolism, particularly branched-chain amino acids causing a buildup of acids which are usually not present. […] Mitochondrial disorders – a group of disorders in which the ability of the body to generate energy is impaired.

• #54 Biochemical Genetics – Seattle Children’s

  https://www.seattlechildrens.org/clinics/genetics/biochemical-genetics/

  In these disorders, complex sugars build up in small sections inside cells, called lysosomes. The buildup makes the cells swell and stops the cells from working right. […] These disorders affect how the body makes energy. They can involve many body systems. Most often they affect the heart, brain and muscles. […] In these disorders, either the body does not make peroxisomes or they do not work right. The disorders can affect many body systems. […] Children with these disorders cannot use protein for energy. This can cause toxic acids to build up in their bodies. […] Children with an amino acid disorder may have trouble breaking down certain amino acids or getting the amino acids into their cells. […] Children with these disorders cannot use protein properly for energy. This can cause toxic by-products to build up in their bodies.

• #55 What Are Metabolic Disorders, and How Can They Cause Epilepsy? | MyEpilepsyTeam

  https://www.myepilepsyteam.com/resources/what-are-metabolic-disorders-and-how-can-they-cause-epilepsy

  Metabolic disorders have been linked to epileptic seizures. […] Genetic mutations that cause metabolic disorders tend to be passed from one generation to the next (inherited). […] Gaucher disease is a genetic disorder caused by mutations in the GBA gene. […] Our bodies are so sensitive to changes in metabolism that problems with just one of these enzymes or proteins can be disastrous. […] Because a breakdown of metabolic processes can directly lead to epilepsy, it is important to recognize the metabolic disorder and treat it to reduce (or even eliminate) seizures. […] Each of these metabolic disorders has unique genetic causes and associated symptoms, but they all cause seizures. […] Biotinidase deficiency and holocarboxylase synthetase deficiency are both inherited disorders that affect the way the body processes a vitamin called biotin (vitamin H).

• #56 Metabolic disorders: Types, causes, and symptoms

  https://www.medicalnewstoday.com/articles/metabolic-disorders

  Metabolic disorders are conditions that affect any aspect of metabolism. […] A metabolic disorder occurs when abnormal chemical reactions disrupt the body’s metabolism. This could affect how well the body can break down large molecules for energy, how efficiently cells can produce energy or cause problems with energy regulation. […] Metabolism is a complex process that involves many biochemicals, tissues, and organs. This means there are many opportunities for something to go wrong and cause a metabolic disorder. Some examples of causes are: […] Genetics: Genes can influence metabolic processes in a variety of ways. For example, people with Gauchers disease have a genetic mutation that limits the production of glucocerebrosidase, an enzyme for breaking down fats. […] It is not always clear what causes a metabolic disorder. For example, type 1 diabetes results from the immune system mistakenly attacking cells in the pancreas. However, medical professionals are not sure what causes this problem with the immune system. […] Metabolic disorders affect some aspects of metabolism, which can result in a range of symptoms or complications. They typically occur due to the body producing too much or too little of a substance. Genetic mutations affecting biochemical processes are the cause of many metabolic disorders.

• #57 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Symptoms are due to the inability to release glucose from the liver and severely impaired glycogenolysis and glucogenesis. […] Disorders of insulin secretion and signaling have pancreatic symptoms varying from hypoplasia in Beckwith-Wiedemann syndrome to endocrine pancreatic dysfunction in RFX6 deficiency. […] Primary mitochondrial disorders (PMD) represent a group of defects of mitochondrial biogenesis or function, caused by inherited or sporadic variants in mitochondrial DNA (mtDNA) or in nuclear-encoded genes necessary for mitochondrial function. […] GI symptoms are a relatively common yet often overlooked feature of many primary mitochondrial disorders, affecting approximately 15% of patients with MtDNA disease. […] Although GI manifestations are not the primary feature of most MIDs, gut dysmotility predominates the clinical presentation in most cases of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

• #58 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Symptoms are due to the inability to release glucose from the liver and severely impaired glycogenolysis and glucogenesis. […] Disorders of insulin secretion and signaling have pancreatic symptoms varying from hypoplasia in Beckwith-Wiedemann syndrome to endocrine pancreatic dysfunction in RFX6 deficiency. […] Primary mitochondrial disorders (PMD) represent a group of defects of mitochondrial biogenesis or function, caused by inherited or sporadic variants in mitochondrial DNA (mtDNA) or in nuclear-encoded genes necessary for mitochondrial function. […] GI symptoms are a relatively common yet often overlooked feature of many primary mitochondrial disorders, affecting approximately 15% of patients with MtDNA disease. […] Although GI manifestations are not the primary feature of most MIDs, gut dysmotility predominates the clinical presentation in most cases of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

• #59 Biochemical Genetics – Seattle Children’s

  https://www.seattlechildrens.org/clinics/genetics/biochemical-genetics/

  In these disorders, complex sugars build up in small sections inside cells, called lysosomes. The buildup makes the cells swell and stops the cells from working right. […] These disorders affect how the body makes energy. They can involve many body systems. Most often they affect the heart, brain and muscles. […] In these disorders, either the body does not make peroxisomes or they do not work right. The disorders can affect many body systems. […] Children with these disorders cannot use protein for energy. This can cause toxic acids to build up in their bodies. […] Children with an amino acid disorder may have trouble breaking down certain amino acids or getting the amino acids into their cells. […] Children with these disorders cannot use protein properly for energy. This can cause toxic by-products to build up in their bodies.

• #60 Biochemical Genetics – Seattle Children’s

  https://www.seattlechildrens.org/clinics/genetics/biochemical-genetics/

  In these disorders, complex sugars build up in small sections inside cells, called lysosomes. The buildup makes the cells swell and stops the cells from working right. […] These disorders affect how the body makes energy. They can involve many body systems. Most often they affect the heart, brain and muscles. […] In these disorders, either the body does not make peroxisomes or they do not work right. The disorders can affect many body systems. […] Children with these disorders cannot use protein for energy. This can cause toxic acids to build up in their bodies. […] Children with an amino acid disorder may have trouble breaking down certain amino acids or getting the amino acids into their cells. […] Children with these disorders cannot use protein properly for energy. This can cause toxic by-products to build up in their bodies.

• #61 What Are Metabolic Disorders, and How Can They Cause Epilepsy? | MyEpilepsyTeam

  https://www.myepilepsyteam.com/resources/what-are-metabolic-disorders-and-how-can-they-cause-epilepsy

  The folate deficiency is caused by dysfunctions in the protein needed to activate it. […] Glucose transporter type 1 deficiency is caused by a genetic mutation that results in a shortage of brain glucose. […] Mitochondrial disorders result when mitochondria are affected by genetic mutations. […] Mitochondrial disorders are the most common group of inherited metabolic disorders. […] Peroxisomal disorders refer to diseases that affect peroxisomes. […] Other metabolic disorders associated with epilepsy include: Urea cycle disorders, congenital disorders of glycosylation, and lysosomal disorders.

• #62 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Pancreatitis can be a complication in citrin deficiency, maple syrup urine disease (types 1a, 1b, and 2), isovaleric acidemia, hydroxymethylglutaric aciduria, propionic acidemia, methylmalonic aciduria, and -ketothiolase deficiency, disorders in which acidosis, ketosis, vomiting, and abdominal pain are common during crises of metabolic decompensation. […] Symptoms of biotinidase deficiency derive from the patients inability to reutilize biotin. […] Feeding difficulties, vomiting, diarrhea, glossitis, and stomatitis may be seen. […] The most common types of inborn errors of carbohydrate metabolism are glycogen storage diseases (GSD) and inborn errors of galactose and fructose metabolism. […] Patients with GSD with liver involvement present in infancy with a tendency toward hypoglycemia, which can be severe in fasting, and marked hepatomegaly.

• #63 Metabolic and genetic disorders mimicking cerebral palsy | Neurosciences Journal

  https://nsj.org.sa/content/24/3/155

  Biotinidase deficiency is an autosomal recessive inherited form of multiple carboxylase deficiency. […] Arginase deficiency is an autosomal recessive urea cycle disorder. […] Aicardi-Goutires syndrome is a genetically inherited autoimmune-mediated encephalopathy. […] Dyskinesia is defined as abnormal involuntary movements, with fluctuating patterns of tone and posture. […] GCH1-related dopa-responsive dystonia is commonly misdiagnosed as CP. […] Sepiapterin reductase deficiency is an autosomal recessive disorder caused by mutation in the sepiapterin reductase gene. […] Glutaric aciduria type 1 is a rare autosomal recessive metabolic disorder caused by alteration in the glutaryl-CoA dehydrogenase gene (GCDH). […] Cerebral creatine deficiency syndromes are a group of the creatine synthesis and transport with 3 recognized syndromes: guanidinoacetate methyltransferase (GAMT), arginine glycine amidinotransferase (AGAT), and X-linked creatine transporter deficiency (SLC6A8).

• #64 Metabolic disorders

  https://bwc.nhs.uk/metabolic-disorders/

  Galactosaemia – a rare genetic metabolic disorder affecting the body’s ability to metabolise the milk sugar, galactose properly. […] Urea cycle defects – genetic disorders caused by a deficiency of one of the enzymes in the urea cycle, responsible for removing ammonia from the bloodstream. […] Familial hypercholesterolaemia (FH) – a condition where there are abnormally high levels of cholesterol in the blood. […] Congenital disorders of glycosylation (CDG) – a group of rare metabolic diseases caused by defects in how sugar side chains are added to proteins. […] Lysosomal storage disorders (LSD) – enzyme deficiencies in the breakdown of complex molecules. […] Organic acidemias – a group of metabolic disorders which disrupts the normal amino acid metabolism, particularly branched-chain amino acids causing a buildup of acids which are usually not present. […] Mitochondrial disorders – a group of disorders in which the ability of the body to generate energy is impaired.

• #65 Metabolic disorders

  https://bwc.nhs.uk/metabolic-disorders/

  Galactosaemia – a rare genetic metabolic disorder affecting the body’s ability to metabolise the milk sugar, galactose properly. […] Urea cycle defects – genetic disorders caused by a deficiency of one of the enzymes in the urea cycle, responsible for removing ammonia from the bloodstream. […] Familial hypercholesterolaemia (FH) – a condition where there are abnormally high levels of cholesterol in the blood. […] Congenital disorders of glycosylation (CDG) – a group of rare metabolic diseases caused by defects in how sugar side chains are added to proteins. […] Lysosomal storage disorders (LSD) – enzyme deficiencies in the breakdown of complex molecules. […] Organic acidemias – a group of metabolic disorders which disrupts the normal amino acid metabolism, particularly branched-chain amino acids causing a buildup of acids which are usually not present. […] Mitochondrial disorders – a group of disorders in which the ability of the body to generate energy is impaired.

• #66 Biochemical Genetics – Seattle Children’s

  https://www.seattlechildrens.org/clinics/genetics/biochemical-genetics/

  Inherited conditions that disrupt how the body makes or uses proteins, fats or carbohydrates are called biochemical genetic disorders. Other names for these are inherited metabolic disorders or inborn errors of metabolism. […] In children with inherited metabolic disorders, 1 or more changes in a gene lead to a problem with 1 of these chemical reactions. This can cause symptoms that range from mild to life-threatening. […] There are hundreds of genetic disorders related to metabolism. We treat these and many others. […] Children with these disorders cannot use fats for energy. This can lead to low blood sugar, muscle weakness and heart problems. […] Many building blocks of the body, such as proteins, fats and other molecules, need to have sugars attached to them to work correctly. […] Problems with how a child’s body breaks down or uses carbohydrates can cause a harmful amount of carbohydrate to build up in their body. This can lead to health problems.

• #67 Inherited Metabolic Disorders: Symptoms, Causes, Treatment | Qwark

  https://qwarkhealth.com/conditions/inherited-metabolic-disorders/?srsltid=AfmBOoqLKd7IrG-bLKa-p0tqViRaEX26eopx3RC5efFyeELkaaPUeas2

  Inherited metabolic disorders are a group of genetic conditions that can affect the body`s ability to properly break down food into energy or to eliminate waste products. These disorders are typically caused by a gene mutation that disrupts the normal function of a specific enzyme. […] Genetic factors that contribute to inherited metabolic disorders include mutations in genes that code for enzymes or proteins involved in metabolic pathways, genetic variations that affect how these enzymes are expressed or regulated, and mutations in genes that code for transport proteins that move substances in and out of cells. […] While inherited metabolic disorders are primarily caused by genetic factors, there are some environmental factors that may exacerbate symptoms or contribute to the development of certain disorders. […] Early detection is crucial for the effective management of inherited metabolic disorders because many of these conditions can cause irreversible organ damage if left untreated. […] Early detection and intervention can have a significant impact on the prognosis of inherited metabolic disorders.

• #68 Inborn Errors of Metabolism – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459183/

  Inborn errors of metabolism are inherited disorders caused by mutations in genes coding for proteins that function in metabolism. Most are inherited as autosomal recessive. Rarely, they are autosomal dominant and X-linked. Environmental, epigenetic, and microbiome factors and additional genes are potential modifying etiologic factors in those with inborn errors of metabolism. […] Inborn errors of metabolism are a heterogeneous group of disorders that may be inherited or may occur as the result of spontaneous mutations. These diseases involve failure of the metabolic pathways involved in either the break-down or storage of carbohydrates, fatty acids, and proteins.

• #69 Metabolic Disorders: Causes, Symptoms and Treatment – CritiCare Hospital

  https://www.criticarehospital.co.in/metabolic-disorders-causes-symptoms-and-treatment/

  Our body consists of a few chemical processes which help digestive enzymes to break down food and convert it into energy that is involved in body functions and keeps you alive. But when the process of metabolism fails and the body starts storing excess, then our body faces a deficiency of several nutrients which keep us healthy. From genetic mutations to other factors, the causes of metabolic disorders are many. […] There are many inherited metabolic disorders such as Type I II Diabetes, Gauchers disease, Inborn Errors of Metabolism, Glucose galactose malabsorption, Phenylketonuria, and others. […] Metabolic disorders may occur due to mutations in genes which can lead to issues in enzymes which are essential for metabolic track. Genetic issues can result in many metabolic disorders which pass down from one generation to another such as sickle cell anaemia, cystic fibrosis, hemochromatosis, and more. Other than genes issues, and environmental issues, exposure to toxins can also lead to metabolic disorders.

• #70 Metabolic Disorders: MedlinePlus

  https://medlineplus.gov/metabolicdisorders.html

  Metabolic disorders occur when abnormal chemical reactions in your body disrupt this process. […] You can develop a metabolic disorder when some organs, such as your liver or pancreas, become diseased or do not function normally.

• #71 The Reciprocal Interplay between Infections and Inherited Metabolic Disorders

  https://www.mdpi.com/2076-2607/11/10/2545

  Infections represent the main cause of acute metabolic derangements and/or the worsening of the clinical course of many inherited metabolic disorders (IMDs). […] Classically, infections have been considered as the consequence of a compromised immune system due to a biochemical defect of energy production. […] An adjunctive pathogenetic mechanism is related to a genetically altered protein-attached glycans composition, due to congenital glycosilation defects. […] Intercurrent infections are the most common trigger of acute metabolic decompensation (AMD) due to the increased metabolic demand during infection, leading to a catabolic state. […] The reason behind this close relationship can be, first of all, attributed to the fact that infections represent a stimulus to the functioning of the immune system, which is a large user of energy, whose production and recycling is essential for its correct functioning.

• #72 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Pancreatitis can be a complication in citrin deficiency, maple syrup urine disease (types 1a, 1b, and 2), isovaleric acidemia, hydroxymethylglutaric aciduria, propionic acidemia, methylmalonic aciduria, and -ketothiolase deficiency, disorders in which acidosis, ketosis, vomiting, and abdominal pain are common during crises of metabolic decompensation. […] Symptoms of biotinidase deficiency derive from the patients inability to reutilize biotin. […] Feeding difficulties, vomiting, diarrhea, glossitis, and stomatitis may be seen. […] The most common types of inborn errors of carbohydrate metabolism are glycogen storage diseases (GSD) and inborn errors of galactose and fructose metabolism. […] Patients with GSD with liver involvement present in infancy with a tendency toward hypoglycemia, which can be severe in fasting, and marked hepatomegaly.

• #73 The Reciprocal Interplay between Infections and Inherited Metabolic Disorders

  https://www.mdpi.com/2076-2607/11/10/2545

  Infections represent the main cause of acute metabolic derangements and/or the worsening of the clinical course of many inherited metabolic disorders (IMDs). […] Classically, infections have been considered as the consequence of a compromised immune system due to a biochemical defect of energy production. […] An adjunctive pathogenetic mechanism is related to a genetically altered protein-attached glycans composition, due to congenital glycosilation defects. […] Intercurrent infections are the most common trigger of acute metabolic decompensation (AMD) due to the increased metabolic demand during infection, leading to a catabolic state. […] The reason behind this close relationship can be, first of all, attributed to the fact that infections represent a stimulus to the functioning of the immune system, which is a large user of energy, whose production and recycling is essential for its correct functioning.

• #74 The Reciprocal Interplay between Infections and Inherited Metabolic Disorders

  https://www.mdpi.com/2076-2607/11/10/2545

  For these reasons, metabolic disorders of energy production potentially function as immunopathies predisposing to different kinds of infections. […] However, the link between infections and IMDs may involve other pathogenetic mechanisms of different cellular pathways, with infective agents functioning as effect or cause of the metabolic derangement. […] Infections are a well-known trigger for FAOD metabolic decompensation. […] Infections can also worsen the clinical course of IMDs not subjected to AMD, provoking chronic disruption of metabolic parameters and an unsatisfactory clinical outcome. […] The data reviewed here strongly suggest that the role of infections in many types of IMDs deserves greater attention for a better management of these disorders and a more focused therapeutic approach.

• #75 Metabolic disease | Definition, Origins, Types, & Facts | Britannica

  https://www.britannica.com/science/metabolic-disease

  metabolic diseases are typically hereditary, yet most persons affected by them may appear healthy for days, months, or even years. […] The onset of symptoms usually occurs when the body’s metabolism comes under stress for example, after prolonged fasting or during a febrile illness. […] In 1908 British physician Sir Archibald Garrod postulated that four inherited conditions of lifelong duration kaptonuria, pentosuria, albinism, and cystinuria were caused by defects in specific biochemical pathways due to the diminished activity or complete lack of a given enzyme. […] He called these disorders inborn errors of metabolism. […] Although Garrod was incorrect in his categorization of cystinuria, his insights provided the field of biochemical genetics with a solid foundation, and the list of inherited inborn errors of metabolism has rapidly grown.

• #76 Metabolic Disorders | Kennedy Krieger Institute

  https://www.kennedykrieger.org/patient-care/conditions/metabolic-disorders

  Genetic metabolic diseases are congenital errors of the body’s chemistry that affect the way in which food is assimilated, energy generated and tissue growth enabled. […] Most metabolic disorders are caused by the genetic deficiency of an enzyme that is needed to convert one chemical into another. […] The deficiency of phenylalanine hydroxylase leads to the accumulation of a toxic level of phenylalanine and a deficiency of tyrosine, both of which damage the developing brain and cause severe intellectual disabilities. […] Other adverse effects of metabolic diseases include seizures, movement disorders, poor growth, muscle weakness, fasting intolerance and disproportionate illness with simple childhood infections or immunizations. […] Some metabolic diseases become manifest in the first few days of life, whereas others require a stress, such as a fever or fasting during an illness, to become manifest. […] Although each metabolic disease individually is rare, there are more than 1,300 known metabolic diseases, and collectively they represent a significant cause of illness and disability in children.

• #77 Inherited Metabolic Disorders Care at OHSU

  https://www.ohsu.edu/doernbecher/inherited-metabolic-disorders

  OHSU Doernbecher Childrens Hospital provides state-of-the art care for people with inherited metabolic disorders. We offer: […] Inherited metabolic disorders are genetic conditions. When someone is diagnosed with one, family members may need to be tested. […] Most inherited metabolic disorders happen when someone inherits a gene that has changed. […] Symptoms can begin before birth or a few weeks after. Sometimes symptoms don’t appear until late childhood or adulthood. […] Inherited metabolic disorders often can’t be cured. In most cases, people have them for life. We focus on getting metabolism as close to normal as possible.

• #78 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Inherited metabolic disorders presenting with gastrointestinal (GI) symptoms are characterized by the dysfunction of the esophagus, stomach, small and large intestines, and pancreas. […] Inherited metabolic diseases (IMDs) are a heterogeneous group of disorders in which pathogenic variants related to metabolic genes lead to an enzymatic deficiency, a defect in a transporter or molecular chaperone, channel dysregulation, or trafficking molecule dysfunction. […] The clinical phenotype in these disorders is due to an abnormal accumulation of substrate and/or a subsequent deficiency of the product of the blocked metabolic step. […] Many inherited metabolic disorders present with gastrointestinal (GI) manifestations, which should be taken into consideration when evaluating a patient. […] The combination of metabolic manifestations accompanied by persistent and difficult-to-mitigate GI symptoms should prompt the evaluating physician to include IMD when considering differential diagnoses.

• #79 Inherited Metabolic Disorders: Types, Signs, Causes & Treatment

  https://www.webmd.com/a-to-z-guides/inherited-metabolic-disorder-types-and-treatments

  Each inherited metabolic disorder is very rare in the general population. But considered together, inherited metabolic disorders may affect about 1 in 1,000 to 2,500 newborns. In certain ethnic populations, such as in Ashkenazi Jews with central and eastern European ancestry, the rate of inherited metabolic disorders is higher.

• #80 Acute Encephalopathy Caused by Inherited Metabolic Diseases

  https://www.mdpi.com/2077-0383/12/11/3797

  Acute encephalopathy is a critical medical condition that typically affects previously healthy children and young adults and often results in death or severe neurological sequelae. Inherited metabolic diseases that can cause acute encephalopathy include urea cycle disorders, amino acid metabolism disorders, organic acid metabolism disorders, fatty acid metabolism disorders, mutations in the thiamine-transporter gene, and mitochondrial diseases. […] Inherited metabolic diseases are caused by genetic mutations that result in quantitative or qualitative abnormalities in enzymes or coenzymes, leading to the accumulation of substances that should be metabolized or a deficiency of substances essential for certain metabolic pathways. Each inherited metabolic disease is a rare disorder, but its overall incidence has been reported to be 1 in 800–2500 patients.

• #81 Inherited Metabolic Disorders | Diabetes Symptoms & Causes

  https://tap.health/metabolic-disorders-diabetes/

  Research shows a strong correlation between a mother’s gestational diabetes and the child’s future risk of developing Type 2 diabetes; children born to mothers with gestational diabetes are 7x more likely to develop Type 2 diabetes later in life. […] Genetic testing can play a vital role in early detection and preventative measures. By identifying specific genes linked to diabetes susceptibility, individuals can understand their personal risk profile.

• #82 Metabolic disease | Definition, Origins, Types, & Facts | Britannica

  https://www.britannica.com/science/metabolic-disease

  If an enzyme is missing or has diminished activity, the pathway becomes blocked, and the formation of the final product is deficient, resulting in disease. […] Low activity of an enzyme may result in the subsequent accumulation of the enzyme’s substrate, which may be toxic at high levels. […] The consequences of metabolic imbalance may be severe; intellectual disability, seizures, decreased muscle tone, organ failure, blindness, and deafness may occur, depending on which enzyme is dysfunctional.

• #83 Metabolic Disorders | Kennedy Krieger Institute

  https://www.kennedykrieger.org/patient-care/conditions/metabolic-disorders

  Genetic metabolic diseases are congenital errors of the body’s chemistry that affect the way in which food is assimilated, energy generated and tissue growth enabled. […] Most metabolic disorders are caused by the genetic deficiency of an enzyme that is needed to convert one chemical into another. […] The deficiency of phenylalanine hydroxylase leads to the accumulation of a toxic level of phenylalanine and a deficiency of tyrosine, both of which damage the developing brain and cause severe intellectual disabilities. […] Other adverse effects of metabolic diseases include seizures, movement disorders, poor growth, muscle weakness, fasting intolerance and disproportionate illness with simple childhood infections or immunizations. […] Some metabolic diseases become manifest in the first few days of life, whereas others require a stress, such as a fever or fasting during an illness, to become manifest. […] Although each metabolic disease individually is rare, there are more than 1,300 known metabolic diseases, and collectively they represent a significant cause of illness and disability in children.

• #84 Inherited Metabolic Disorders: Overview and Resources

  https://metab.ern-net.eu/inherited-metabolic-disorders/

  Inherited Metabolic Disorders (IMDs), in particular, represent a group of more than 1400 rare genetic pathologies, classified in 130 different biochemical groups, that impact both children and adults and are quite heterogeneous. […] Metabolic disorders are generally chronic and progressive and can involve multiple organs, thus early diagnosis and treatment are crucial to avoid further complications. […] IMDs are a complex class of conditions that can affect the metabolism of carbohydrates, amino acids, lipids, steroids but also nucleic acids, mitochondria and neurotransmitters. […] Disorders of intermediary metabolism involve pathways that mediate the breakdown of low-molecular weight nutrient compounds (such as proteins, carbohydrates, and lipids) or convert them into substrates for the biosynthesis of complex molecules.

• #85 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Inherited metabolic disorders presenting with gastrointestinal (GI) symptoms are characterized by the dysfunction of the esophagus, stomach, small and large intestines, and pancreas. […] Inherited metabolic diseases (IMDs) are a heterogeneous group of disorders in which pathogenic variants related to metabolic genes lead to an enzymatic deficiency, a defect in a transporter or molecular chaperone, channel dysregulation, or trafficking molecule dysfunction. […] The clinical phenotype in these disorders is due to an abnormal accumulation of substrate and/or a subsequent deficiency of the product of the blocked metabolic step. […] Many inherited metabolic disorders present with gastrointestinal (GI) manifestations, which should be taken into consideration when evaluating a patient. […] The combination of metabolic manifestations accompanied by persistent and difficult-to-mitigate GI symptoms should prompt the evaluating physician to include IMD when considering differential diagnoses.

• #86 Acute Encephalopathy Caused by Inherited Metabolic Diseases

  https://www.mdpi.com/2077-0383/12/11/3797

  Acute encephalopathy is a critical medical condition that typically affects previously healthy children and young adults and often results in death or severe neurological sequelae. Inherited metabolic diseases that can cause acute encephalopathy include urea cycle disorders, amino acid metabolism disorders, organic acid metabolism disorders, fatty acid metabolism disorders, mutations in the thiamine-transporter gene, and mitochondrial diseases. […] Inherited metabolic diseases are caused by genetic mutations that result in quantitative or qualitative abnormalities in enzymes or coenzymes, leading to the accumulation of substances that should be metabolized or a deficiency of substances essential for certain metabolic pathways. Each inherited metabolic disease is a rare disorder, but its overall incidence has been reported to be 1 in 800–2500 patients.

• #87 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Leigh disease usually presents in infancy or early childhood with CNS symptoms and characteristic symmetrical findings in the basal ganglia and brain stem seen on brain imaging; adult cases are rare, but have been reported. […] Although the etiology of the GI dysfunction in Leigh syndrome is unknown, it has been postulated that the autonomic nerve supply to the GI tract could be affected by necrosis in the brain stem and spinal cord. […] Malabsorption, failure to thrive, abdominal pain, and pancreatitis are characteristic of disorders of lipoprotein metabolism. […] Disorders of bile acid synthesis commonly present with neonatal cholestasis followed by diarrhea, steatorrhea, and malabsorption of the fat-soluble vitamins A, D, E and K. […] The common gastrointestinal symptoms found in bile acids biosynthesis disorders are due to the reduced capability to properly digest and breakdown and absorb lipid macromolecules in the digestive system, leading to a decrease in the stool consistency.

• #88 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Leigh disease usually presents in infancy or early childhood with CNS symptoms and characteristic symmetrical findings in the basal ganglia and brain stem seen on brain imaging; adult cases are rare, but have been reported. […] Although the etiology of the GI dysfunction in Leigh syndrome is unknown, it has been postulated that the autonomic nerve supply to the GI tract could be affected by necrosis in the brain stem and spinal cord. […] Malabsorption, failure to thrive, abdominal pain, and pancreatitis are characteristic of disorders of lipoprotein metabolism. […] Disorders of bile acid synthesis commonly present with neonatal cholestasis followed by diarrhea, steatorrhea, and malabsorption of the fat-soluble vitamins A, D, E and K. […] The common gastrointestinal symptoms found in bile acids biosynthesis disorders are due to the reduced capability to properly digest and breakdown and absorb lipid macromolecules in the digestive system, leading to a decrease in the stool consistency.

• #89 Treatable inherited metabolic epilepsies | Neurosciences Journal

  https://nsj.org.sa/content/26/3/229

  Inherited metabolic diseases usually present a complex clinical picture in which seizures are one of various neurological manifestations, which include developmental delays/regression, acute encephalopathy, neuropsychiatric manifestations, and movement disorders. […] The specific diagnosis of an underlying inherited metabolic disorder in epileptic patients may help design specific treatments that can improve the seizures and stop neurodegeneration. […] Early diagnosis of an underlying treatable inherited metabolic disease as a cause of epilepsy is crucial since many will require specific management beyond common anti-seizure drugs, either to control seizures or to decrease the risk of brain injury. […] The mechanisms of seizure generation in inherited metabolic disorders are diverse.

• #90 Treatable inherited metabolic epilepsies | Neurosciences Journal

  https://nsj.org.sa/content/26/3/229

  Inherited metabolic diseases usually present a complex clinical picture in which seizures are one of various neurological manifestations, which include developmental delays/regression, acute encephalopathy, neuropsychiatric manifestations, and movement disorders. […] The specific diagnosis of an underlying inherited metabolic disorder in epileptic patients may help design specific treatments that can improve the seizures and stop neurodegeneration. […] Early diagnosis of an underlying treatable inherited metabolic disease as a cause of epilepsy is crucial since many will require specific management beyond common anti-seizure drugs, either to control seizures or to decrease the risk of brain injury. […] The mechanisms of seizure generation in inherited metabolic disorders are diverse.

• #91 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  We have identified 339 IMDs associated with various types of GI involvement which we classified into seven groups according to the lesion site of the GI system. […] Feeding difficulties represent the most common abnormality reported for IMDs with GI involvement (127/339; 37%) followed by intestinal problems (103/339; 30%), vomiting (75/339; 22%), stomach and pancreas involvement (28/339; 8% each), and esophagus involvement (15/339; 4%). […] Failure to thrive is common among individuals with an IMD involving nitrogen-containing compounds. […] Vomiting and feeding difficulties are also commonly observed, as many affected individuals cannot tolerate protein ingestion and must follow a protein restricted diet. […] Chronic vomiting is a characteristic feature among branched-chain organic acidurias and urea cycle disorders in which hyperammonemia occurs.

• #92 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  We have identified 339 IMDs associated with various types of GI involvement which we classified into seven groups according to the lesion site of the GI system. […] Feeding difficulties represent the most common abnormality reported for IMDs with GI involvement (127/339; 37%) followed by intestinal problems (103/339; 30%), vomiting (75/339; 22%), stomach and pancreas involvement (28/339; 8% each), and esophagus involvement (15/339; 4%). […] Failure to thrive is common among individuals with an IMD involving nitrogen-containing compounds. […] Vomiting and feeding difficulties are also commonly observed, as many affected individuals cannot tolerate protein ingestion and must follow a protein restricted diet. […] Chronic vomiting is a characteristic feature among branched-chain organic acidurias and urea cycle disorders in which hyperammonemia occurs.

• #93 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Leigh disease usually presents in infancy or early childhood with CNS symptoms and characteristic symmetrical findings in the basal ganglia and brain stem seen on brain imaging; adult cases are rare, but have been reported. […] Although the etiology of the GI dysfunction in Leigh syndrome is unknown, it has been postulated that the autonomic nerve supply to the GI tract could be affected by necrosis in the brain stem and spinal cord. […] Malabsorption, failure to thrive, abdominal pain, and pancreatitis are characteristic of disorders of lipoprotein metabolism. […] Disorders of bile acid synthesis commonly present with neonatal cholestasis followed by diarrhea, steatorrhea, and malabsorption of the fat-soluble vitamins A, D, E and K. […] The common gastrointestinal symptoms found in bile acids biosynthesis disorders are due to the reduced capability to properly digest and breakdown and absorb lipid macromolecules in the digestive system, leading to a decrease in the stool consistency.

• #94 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Leigh disease usually presents in infancy or early childhood with CNS symptoms and characteristic symmetrical findings in the basal ganglia and brain stem seen on brain imaging; adult cases are rare, but have been reported. […] Although the etiology of the GI dysfunction in Leigh syndrome is unknown, it has been postulated that the autonomic nerve supply to the GI tract could be affected by necrosis in the brain stem and spinal cord. […] Malabsorption, failure to thrive, abdominal pain, and pancreatitis are characteristic of disorders of lipoprotein metabolism. […] Disorders of bile acid synthesis commonly present with neonatal cholestasis followed by diarrhea, steatorrhea, and malabsorption of the fat-soluble vitamins A, D, E and K. […] The common gastrointestinal symptoms found in bile acids biosynthesis disorders are due to the reduced capability to properly digest and breakdown and absorb lipid macromolecules in the digestive system, leading to a decrease in the stool consistency.

• #95 Inherited Metabolic Diseases » Hepatitis B Foundation

  https://www.hepb.org/research-and-programs/liver/risk-factors-for-liver-cancer/inherited-metabolic-diseases/

  Some inherited diseases that result in liver damage and cirrhosis may increase the risk of liver cancer. […] People who have hemochromatosis absorb too much iron from their food. The excess iron can build up in the liver, causing cirrhosis that may lead to liver cancer. […] This genetic disorder is caused by a shortage of one of the enzymes needed to break down tyrosine, a building block of many proteins. Build-up of tyrosine in the liver can lead to liver failure and possibly liver cancer. […] People who have a shortage of AAT can develop liver disease and ultimately liver cancer. […] People with PCT store too many porphyrins in their liver, which stops the liver from working properly. This can result in cirrhosis and even liver cancer. […] Because glycogen is stored in the liver, GSD can cause liver disease. […] The copper builds up in an affected persons liver, resulting in liver disease and sometimes even acute liver failure.

• #96 Inherited Metabolic Diseases » Hepatitis B Foundation

  https://www.hepb.org/research-and-programs/liver/risk-factors-for-liver-cancer/inherited-metabolic-diseases/

  Some inherited diseases that result in liver damage and cirrhosis may increase the risk of liver cancer. […] People who have hemochromatosis absorb too much iron from their food. The excess iron can build up in the liver, causing cirrhosis that may lead to liver cancer. […] This genetic disorder is caused by a shortage of one of the enzymes needed to break down tyrosine, a building block of many proteins. Build-up of tyrosine in the liver can lead to liver failure and possibly liver cancer. […] People who have a shortage of AAT can develop liver disease and ultimately liver cancer. […] People with PCT store too many porphyrins in their liver, which stops the liver from working properly. This can result in cirrhosis and even liver cancer. […] Because glycogen is stored in the liver, GSD can cause liver disease. […] The copper builds up in an affected persons liver, resulting in liver disease and sometimes even acute liver failure.

• #97 Inherited Metabolic Diseases » Hepatitis B Foundation

  https://www.hepb.org/research-and-programs/liver/risk-factors-for-liver-cancer/inherited-metabolic-diseases/

  Some inherited diseases that result in liver damage and cirrhosis may increase the risk of liver cancer. […] People who have hemochromatosis absorb too much iron from their food. The excess iron can build up in the liver, causing cirrhosis that may lead to liver cancer. […] This genetic disorder is caused by a shortage of one of the enzymes needed to break down tyrosine, a building block of many proteins. Build-up of tyrosine in the liver can lead to liver failure and possibly liver cancer. […] People who have a shortage of AAT can develop liver disease and ultimately liver cancer. […] People with PCT store too many porphyrins in their liver, which stops the liver from working properly. This can result in cirrhosis and even liver cancer. […] Because glycogen is stored in the liver, GSD can cause liver disease. […] The copper builds up in an affected persons liver, resulting in liver disease and sometimes even acute liver failure.

• #98 Biochemical Genetics – Seattle Children’s

  https://www.seattlechildrens.org/clinics/genetics/biochemical-genetics/

  Children with a purine or pyrimidine metabolism disorder could have problems with their learning, behavior, immune system or growth. […] Children with Wilson disease cannot get rid of copper they get from food but do not need. Most children’s bodies filter out this extra copper. But in children with Wilson disease, the copper builds up and can damage their liver, brain and other organs.

• #99 Inherited Metabolic Disorders: Symptoms, Causes, Treatment | Qwark

  https://qwarkhealth.com/conditions/inherited-metabolic-disorders/?srsltid=AfmBOoqLKd7IrG-bLKa-p0tqViRaEX26eopx3RC5efFyeELkaaPUeas2

  Inherited metabolic disorders are a group of genetic conditions that can affect the body`s ability to properly break down food into energy or to eliminate waste products. These disorders are typically caused by a gene mutation that disrupts the normal function of a specific enzyme. […] Genetic factors that contribute to inherited metabolic disorders include mutations in genes that code for enzymes or proteins involved in metabolic pathways, genetic variations that affect how these enzymes are expressed or regulated, and mutations in genes that code for transport proteins that move substances in and out of cells. […] While inherited metabolic disorders are primarily caused by genetic factors, there are some environmental factors that may exacerbate symptoms or contribute to the development of certain disorders. […] Early detection is crucial for the effective management of inherited metabolic disorders because many of these conditions can cause irreversible organ damage if left untreated. […] Early detection and intervention can have a significant impact on the prognosis of inherited metabolic disorders.

• #100 Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features – UpToDate

  https://www.uptodate.com/contents/inborn-errors-of-metabolism-epidemiology-pathogenesis-and-clinical-features

  Congenital metabolic disorders result from the absence or abnormality of an enzyme or its cofactor, leading to either accumulation or deficiency of a specific metabolite. Most of these disorders are transmitted as autosomal recessive traits. […] The possibility of an inborn error of metabolism (IEM) should be considered in infants, children, and adults who present with any of the clinical or laboratory features discussed below or in the topic review on metabolic emergencies, particularly if the findings remain unexplained after standard evaluation. […] Optimal outcome for children with IEM depends upon early recognition of the signs and symptoms of metabolic disease and prompt evaluation and referral to a center familiar with the management of these disorders. Delay in diagnosis may result in acute metabolic decompensation, progressive neurologic injury, or death. […] The epidemiology, pathogenesis, and most common chronic clinical and laboratory manifestations of IEM are discussed below.

• #101 Treatable inherited metabolic epilepsies | Neurosciences Journal

  https://nsj.org.sa/content/26/3/229

  Inherited metabolic diseases usually present a complex clinical picture in which seizures are one of various neurological manifestations, which include developmental delays/regression, acute encephalopathy, neuropsychiatric manifestations, and movement disorders. […] The specific diagnosis of an underlying inherited metabolic disorder in epileptic patients may help design specific treatments that can improve the seizures and stop neurodegeneration. […] Early diagnosis of an underlying treatable inherited metabolic disease as a cause of epilepsy is crucial since many will require specific management beyond common anti-seizure drugs, either to control seizures or to decrease the risk of brain injury. […] The mechanisms of seizure generation in inherited metabolic disorders are diverse.

• #102 Treatable inherited metabolic epilepsies | Neurosciences Journal

  https://nsj.org.sa/content/26/3/229

  Inherited metabolic diseases usually present a complex clinical picture in which seizures are one of various neurological manifestations, which include developmental delays/regression, acute encephalopathy, neuropsychiatric manifestations, and movement disorders. […] The specific diagnosis of an underlying inherited metabolic disorder in epileptic patients may help design specific treatments that can improve the seizures and stop neurodegeneration. […] Early diagnosis of an underlying treatable inherited metabolic disease as a cause of epilepsy is crucial since many will require specific management beyond common anti-seizure drugs, either to control seizures or to decrease the risk of brain injury. […] The mechanisms of seizure generation in inherited metabolic disorders are diverse.

• #103 Metabolic Disorders: Diagnosis & Treatment | NewYork-Presbyterian

  https://www.nyp.org/digestive/weight-loss-and-metabolic-disorders/metabolic-disorders/treatment

  Metabolic disorders are usually congenital (present from birth) and can be detected through routine screening. […] If an inherited metabolic disorder is not detected at birth, it can be diagnosed later in life when symptoms appear. […] Once symptoms develop, blood or DNA tests are available to diagnose most genetic metabolic disorders. […] Because metabolic disorders tend to run in families, your doctor will examine your family history for metabolic diseases. […] Tests for many metabolic disorders can be done prenatally before a baby’s birth. […] Genetic tests can be used to help in diagnosing this condition. […] Symptoms of inherited metabolic disorders can also develop after birth.

• #104 Metabolic Disorders: Diagnosis & Treatment | NewYork-Presbyterian

  https://www.nyp.org/digestive/weight-loss-and-metabolic-disorders/metabolic-disorders/treatment

  Metabolic disorders are usually congenital (present from birth) and can be detected through routine screening. […] If an inherited metabolic disorder is not detected at birth, it can be diagnosed later in life when symptoms appear. […] Once symptoms develop, blood or DNA tests are available to diagnose most genetic metabolic disorders. […] Because metabolic disorders tend to run in families, your doctor will examine your family history for metabolic diseases. […] Tests for many metabolic disorders can be done prenatally before a baby’s birth. […] Genetic tests can be used to help in diagnosing this condition. […] Symptoms of inherited metabolic disorders can also develop after birth.

• #105 Metabolic Disorders: Diagnosis & Treatment | NewYork-Presbyterian

  https://www.nyp.org/digestive/weight-loss-and-metabolic-disorders/metabolic-disorders/treatment

  Metabolic disorders are usually congenital (present from birth) and can be detected through routine screening. […] If an inherited metabolic disorder is not detected at birth, it can be diagnosed later in life when symptoms appear. […] Once symptoms develop, blood or DNA tests are available to diagnose most genetic metabolic disorders. […] Because metabolic disorders tend to run in families, your doctor will examine your family history for metabolic diseases. […] Tests for many metabolic disorders can be done prenatally before a baby’s birth. […] Genetic tests can be used to help in diagnosing this condition. […] Symptoms of inherited metabolic disorders can also develop after birth.

• #106 Metabolic Disorders: Diagnosis & Treatment | NewYork-Presbyterian

  https://www.nyp.org/digestive/weight-loss-and-metabolic-disorders/metabolic-disorders/treatment

  Metabolic disorders are usually congenital (present from birth) and can be detected through routine screening. […] If an inherited metabolic disorder is not detected at birth, it can be diagnosed later in life when symptoms appear. […] Once symptoms develop, blood or DNA tests are available to diagnose most genetic metabolic disorders. […] Because metabolic disorders tend to run in families, your doctor will examine your family history for metabolic diseases. […] Tests for many metabolic disorders can be done prenatally before a baby’s birth. […] Genetic tests can be used to help in diagnosing this condition. […] Symptoms of inherited metabolic disorders can also develop after birth.

• #107 Treatable inherited metabolic epilepsies | Neurosciences Journal

  https://nsj.org.sa/content/26/3/229

  Thus, a large proportion of inherited metabolic disorders can present with seizures, either during acute decompensation of the primary metabolic disorder or as a part of the complex phenotype of the inherited metabolic disorder. […] The presence of any of sign and symptom highlighted in Table 2 should raise suspicion for an underlying metabolic etiology of epilepsy. […] The work-up of a patient with a suspected inherited metabolic disease as a cause of epilepsy is based on a combination of EEG, neuroimaging, biochemical and molecular genetic testing. […] A growing number of treatable inherited metabolic disorders associated with epilepsy have been described. […] Early diagnosis and treatment are associated with better outcomes.

• #108 Metabolic and genetic disorders mimicking cerebral palsy | Neurosciences Journal

  https://nsj.org.sa/content/24/3/155

  A growing number of metabolic and genetic disorders may present with symptoms and signs that resemble a CP phenotype. […] The following elements in the patients medical history are not typical for CP and are an important clue to the possibility of CP mimic: absent history of any risk factors leading to brain injury, such as prematurity, perinatal or infantile hypoxic ischemic insult, intracranial bleeding, kernicterus, cerebral vascular accident, infection or head injury, family history of CP, progressive neurological symptoms, regression of milestones, diurnal variation of symptoms or symptoms fluctuation in relation to activity or fasting. […] Brain MRI is recommended as a first-line investigation in all children with a clinical feature suggestive of CP. […] If the findings are normal or nonspecific, other investigations should be carried out to rule out an underlying metabolic or genetic disease.

• #109 Acute Encephalopathy Caused by Inherited Metabolic Diseases

  https://www.mdpi.com/2077-0383/12/11/3797

  When inherited metabolic diseases are suspected, it is imperative to promptly perform metabolic screening tests because diagnosis requires specific tests. Proper diagnosis and treatment ultimately determine a patient’s prognosis. […] Acute encephalopathy due to inherited metabolic diseases can have numerous different causes, and recognition of the possibility of an inherited metabolic disease as early as possible, obtaining appropriate specimens, and proceeding with testing and treatment in parallel are crucial in the management of these diseases.

• #110 Metabolic and genetic disorders mimicking cerebral palsy | Neurosciences Journal

  https://nsj.org.sa/content/24/3/155

  Cerebral palsy is a syndrome that encompasses a large group of childhood movement and posture disorders that result from a lesion occurring in the developing brain. […] The clinical presentation of many metabolic and genetic conditions, particularly in highly consanguineous populations, can mimic cerebral palsy particularly at early age. […] A growing group of metabolic and genetic disorders is being recognized, mainly due to the advancement in the area of metabolic and genetic investigations, to present with exactly the same symptoms and signs as CP. […] The possibility of a treatable metabolic or genetic etiology of CP, together with a more accurate diagnosis and genetic counseling, emphasizes the importance of being particularly vigilant in determining the etiology. […] Inherited metabolic and genetic diseases are common in highly consanguineous populations. Their clinical presentation may be nonspecific or very slowly progressive, especially in the early age. They can therefore be misdiagnosed as CP.

• #111 Inherited metabolic disorders involving the eye: a clinico-biochemical perspective | Eye

  https://www.nature.com/articles/eye2009229

  The diagnosis of inborn errors of metabolism is challenging for most physicians. […] Although there is an extensive understanding of many inborn errors of metabolism at the biochemical, molecular, and metabolic levels, little is known about their pathogenesis. In particular, how systemic metabolic disease contributes to ocular defects remains to be elucidated in IMDs. The occurrence of eye abnormalities could be due to direct toxic mechanisms of abnormal metabolic products or accumulation of normal metabolites by errors of synthetic pathways or by deficient energy metabolism. […] Inborn metabolic disorders constitute a heterogeneous group of disorders affecting the metabolic pathways with an underlying genetic defect. […] The latest discoveries in the human genome project and advances in medical technology have resulted in significant alterations in the diagnosis, classification, and treatment of IMDs.

• #112 Inherited metabolic diseases | Basicmedical Key

  https://basicmedicalkey.com/inherited-metabolic-diseases/

  Because they are individually rare, it is important for the clinician to have a high index of suspicion and actively consider the possibility that an illness may be caused by an inherited metabolic disease. […] The techniques of molecular genetic analysis are now also being increasingly used in the screening and diagnosis of inherited metabolic diseases. […] Glucose 6-phosphatase deficiency exemplifies the development of a clinical syndrome due to lack of formation of the product of an enzyme-catalysed reaction. […] Glucose 6-phosphatase deficiency also exemplifies the consequences of accumulation of a precursor other than the immediate substrate of the defective enzyme. […] Three enzyme defects can cause galactosaemia, and exemplify the production of a clinical syndrome due to the accumulation of a substrate of the missing enzyme. […] Phenylketonuria (PKU) is another condition in which the accumulation of the substrate of the missing enzyme gives rise to a clinical syndrome. […] The enzyme concerned is phenylalanine hydroxylase, which hydroxylates phenylalanine to form tyrosine.

• #113 Metabolic and genetic disorders mimicking cerebral palsy | Neurosciences Journal

  https://nsj.org.sa/content/24/3/155

  Most of the metabolic/genetic diseases have overlapping or unspecific phenotypes. […] The utility of next-generation sequencing in the clinical field has been widely demonstrated in different groups of diseases, mainly in metabolic/genetic diseases. […] The metabolic and genetic disorders that may misdiagnosed as CP are outlined in Table 3, classified by the most predominant motor pattern, although in many conditions the clinical features are not always pure. […] Several neurometabolic disorders can resemble spastic CP, resulting in misdiagnosis. […] Hereditary spastic paraplegias (HSPs) constitute a wide and heterogeneous group of genetically determined neurodegenerative disorders that share a common clinical feature of lower limb spasticity and muscle weakness. […] COL4A1-related spastic CP is a collagen vascular disorder which may cause an antenatal or perinatal cerebrovascular insult, resulting in a neonatal stroke syndrome that manifests as hemiplegia or quadriplegia.

• #114 New study first to identify an expanded section of DNA as cause of a rare genetic metabolic disorder – UBC Faculty of Medicine

  https://www.med.ubc.ca/news/new-study-first-to-identify-an-expanded-section-of-dna-as-cause-of-a-rare-genetic-metabolic-disorder/

  A new study from BC Childrens Hospital, the University of British Columbia (UBC) and an international team of researchers published in the New England Journal of Medicine is the first to identify a rarely-seen type of DNA mutation as the cause of an inherited metabolic disorder. […] Inherited metabolic disorders where the body cant break down specific nutrients from food leading to a range of serious health problems are often caused by a defective gene. […] In this important study, researchers found an unusual genetic mutation behind three childrens undiagnosed, degenerative conditions: a repeat expansion of DNA. […] The gene identified as the cause of this particular disorder is an enzyme that enables the body to turn an amino acid called glutamine into glutamate. […] More work is needed to determine how exactly this genetic error leads to disease, but its likely that either a build-up of glutamine or the lack of glutamate caused the childrens serious developmental delays and disabilities including difficulty with language, speech, balance and coordination.

• #115 Inherited Metabolic Disorders | Diabetes Symptoms & Causes

  https://tap.health/metabolic-disorders-diabetes/

  Research shows a strong correlation between a mother’s gestational diabetes and the child’s future risk of developing Type 2 diabetes; children born to mothers with gestational diabetes are 7x more likely to develop Type 2 diabetes later in life. […] Genetic testing can play a vital role in early detection and preventative measures. By identifying specific genes linked to diabetes susceptibility, individuals can understand their personal risk profile.

• #116 Inborn Errors of Metabolism (IEM) – Inherited Metabolic Disorders

  https://my.clevelandclinic.org/health/diseases/17962-inherited-metabolic-disorders

  Inborn errors of metabolism, also known as inherited metabolic disorders or hereditary metabolic disorders, are a group of conditions that affect your ability to convert food into energy and remove waste and unhealthy substances from your body. […] A genetic mutation that happens when your cells divide and replicate during fetal development causes inborn errors of metabolism (IEM). […] Several possible genes cause each type of IEM. […] When you have an inborn error of metabolism, your enzymes dont have the instructions they need to do their job within your metabolism, which causes symptoms of the specific IEM that affects your body.

• #117 Inborn Errors of Metabolism: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/804757-overview

  Inborn errors of metabolism describes a class of over 1000 inherited disorders caused by mutations in genes coding for proteins that function in metabolism. Most of the disorders are inherited as autosomal recessive, but some are autosomal dominant or X-linked. […] IEMs were initially thought to be caused by a specific single-gene mutation, but genetic characterization of variation in clinical manifestations led to the understanding that IEMs can be caused by different gene mutations that result in the same or similar diagnostic biochemical abnormalities. […] The presentation of specific IEMs as a spectrum of disease phenotypes in which a clear correlation between the severity of mutation at the affected locus and the phenotype (genotype-phenotype correlation) is often lacking and impacts the ability to predict disease course. […] Additional genes and environmental, epigenetic, and microbiome factors are also potential modifying etiologic factors in individual IEMs.

• #118 Metabolic Disorders: Symptoms & Causes | NewYork-Presbyterian

  https://www.nyp.org/digestive/weight-loss-and-metabolic-disorders/metabolic-disorders

  Inherited metabolic disorders may affect about one in 1,000 to 2,500 newborns. […] Genetic mutations cause hundreds of genetic metabolic disorders passed down from generation to generation. […] Common causes of metabolic disorders are: […] Genetics: Metabolic disorders are caused by genetic defects commonly inherited from both parents. Gaucher’s disease and phenylketonuria (PKU) are examples of inherited metabolic disorders. […] It’s important to be aware of the various risk factors associated with this condition. Individuals with a higher risk for inherited metabolic disorders are primarily those who have a family history of the condition.

• #119 Inborn Errors of Metabolism: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/804757-overview

  Inborn errors of metabolism describes a class of over 1000 inherited disorders caused by mutations in genes coding for proteins that function in metabolism. Most of the disorders are inherited as autosomal recessive, but some are autosomal dominant or X-linked. […] IEMs were initially thought to be caused by a specific single-gene mutation, but genetic characterization of variation in clinical manifestations led to the understanding that IEMs can be caused by different gene mutations that result in the same or similar diagnostic biochemical abnormalities. […] The presentation of specific IEMs as a spectrum of disease phenotypes in which a clear correlation between the severity of mutation at the affected locus and the phenotype (genotype-phenotype correlation) is often lacking and impacts the ability to predict disease course. […] Additional genes and environmental, epigenetic, and microbiome factors are also potential modifying etiologic factors in individual IEMs.

• #120 Clinical and biochemical footprints of inherited metabolic disorders. XI. Gastrointestinal symptoms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10509718/

  Inherited metabolic disorders presenting with gastrointestinal (GI) symptoms are characterized by the dysfunction of the esophagus, stomach, small and large intestines, and pancreas. […] Inherited metabolic diseases (IMDs) are a heterogeneous group of disorders in which pathogenic variants related to metabolic genes lead to an enzymatic deficiency, a defect in a transporter or molecular chaperone, channel dysregulation, or trafficking molecule dysfunction. […] The clinical phenotype in these disorders is due to an abnormal accumulation of substrate and/or a subsequent deficiency of the product of the blocked metabolic step. […] Many inherited metabolic disorders present with gastrointestinal (GI) manifestations, which should be taken into consideration when evaluating a patient. […] The combination of metabolic manifestations accompanied by persistent and difficult-to-mitigate GI symptoms should prompt the evaluating physician to include IMD when considering differential diagnoses.

• #121 Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features – UpToDate

  https://www.uptodate.com/contents/inborn-errors-of-metabolism-epidemiology-pathogenesis-and-clinical-features

  Congenital metabolic disorders result from the absence or abnormality of an enzyme or its cofactor, leading to either accumulation or deficiency of a specific metabolite. Most of these disorders are transmitted as autosomal recessive traits. […] The possibility of an inborn error of metabolism (IEM) should be considered in infants, children, and adults who present with any of the clinical or laboratory features discussed below or in the topic review on metabolic emergencies, particularly if the findings remain unexplained after standard evaluation. […] Optimal outcome for children with IEM depends upon early recognition of the signs and symptoms of metabolic disease and prompt evaluation and referral to a center familiar with the management of these disorders. Delay in diagnosis may result in acute metabolic decompensation, progressive neurologic injury, or death. […] The epidemiology, pathogenesis, and most common chronic clinical and laboratory manifestations of IEM are discussed below.

• #122 Inherited metabolic disorders involving the eye: a clinico-biochemical perspective | Eye

  https://www.nature.com/articles/eye2009229

  The diagnosis of inborn errors of metabolism is challenging for most physicians. […] Although there is an extensive understanding of many inborn errors of metabolism at the biochemical, molecular, and metabolic levels, little is known about their pathogenesis. In particular, how systemic metabolic disease contributes to ocular defects remains to be elucidated in IMDs. The occurrence of eye abnormalities could be due to direct toxic mechanisms of abnormal metabolic products or accumulation of normal metabolites by errors of synthetic pathways or by deficient energy metabolism. […] Inborn metabolic disorders constitute a heterogeneous group of disorders affecting the metabolic pathways with an underlying genetic defect. […] The latest discoveries in the human genome project and advances in medical technology have resulted in significant alterations in the diagnosis, classification, and treatment of IMDs.

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