Materiały źródłowe

• #1 Overview of maple syrup urine disease – UpToDate

  https://www.uptodate.com/contents/overview-of-maple-syrup-urine-disease

  Maple syrup urine disease (MSUD; MIM #248600) also known as branched-chain ketoaciduria, is a disorder affecting the aliphatic or branched-chain amino acids (BCAAs). It is caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase complex (BCKDC), the second enzyme of the metabolic pathway of the three BCAAs, leucine, isoleucine, and valine. […] MSUD is caused by pathogenic variants of genes that encode branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) components E1-alpha, E1-beta, E2, and E3. […] The mode of inheritance is autosomal recessive. […] Homozygous or compound heterozygous variants in any of these genes can cause any of the forms of MSUD. […] There are case reports of a mild form of MSUD due to homozygous variants in the protein phosphatase, Mg2+/Mn2+ dependent 1K (PPM1K) gene encoding the BCKDC phosphatase. […] Pathogenic variants in the gene encoding the BCKDC kinase have not been identified. […] Decreased activity of BCKDC results in elevation of plasma concentrations of the BCAAs (leucine, isoleucine, and valine) and their corresponding keto acids.

• #2 Maple Syrup Urine Disease – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1319/

  Maple syrup urine disease (MSUD) is caused by decreased activity of the branched-chain alpha-ketoacid dehydrogenase complex (BCKD), the second enzymatic step in the degradative pathway of the branched-chain amino acids (BCAAs), which includes leucine, isoleucine, and valine. […] MSUD is a recessive disorder caused by biallelic pathogenic variants in BCKDHA, BCKDHB, or DBT that result in decreased function or loss of function. […] Pathogenic variants in both alleles encoding any subunit can result in decreased activity of the enzyme complex and the accumulation of BCAAs and corresponding BCKAs in tissues and plasma.

• #3 Maple Syrup Urine Disease: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/21168-maple-syrup-urine-disease

  The mutations may appear on any of the three genes responsible for enzymes breaking down the three amino acids. These genes are: BCKDHA, BCKDHB, DBT. […] Its inherited in an autosomal recessive pattern. A child is born with MSUD when both parents are carriers of the specific gene mutation and pass it on. Being a carrier means you have one normal copy of the gene and one mutated copy. Carriers dont develop MSUD. To develop MSUD, you inherit two mutated genes one copy of the altered gene from each parent. […] The way you inherit MSUD is what causes it to be more common in communities where people share similar genes (and similar genetic mutations).

• #4 Maple syrup urine disease – Wikipedia

  https://en.wikipedia.org/wiki/Maple_syrup_urine_disease

  This condition has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene – one from each parent – must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually unaffected by the disorder.

• #5 Maple syrup urine disease

  https://www.nhs.uk/conditions/maple-syrup-urine-disease/

  Maple syrup urine disease (MSUD) is a rare but serious inherited condition. […] The genetic change (mutation) responsible for MSUD is passed on by the parents, who usually do not have any symptoms of the condition. This is called autosomal recessive inheritance. […] This means a baby needs to receive two copies of the altered genes to develop the condition one from their mother and one from their father. If the baby only receives one mutated gene, they’ll just be a carrier of MSUD. […] Although it’s not possible to prevent MSUD, it’s important to let your midwife and doctor know if you have a family history of the condition, so that tests and treatment are given as soon as possible.

• #6 Maple Syrup Urine Disease: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/21168-maple-syrup-urine-disease

  The mutations may appear on any of the three genes responsible for enzymes breaking down the three amino acids. These genes are: BCKDHA, BCKDHB, DBT. […] Its inherited in an autosomal recessive pattern. A child is born with MSUD when both parents are carriers of the specific gene mutation and pass it on. Being a carrier means you have one normal copy of the gene and one mutated copy. Carriers dont develop MSUD. To develop MSUD, you inherit two mutated genes one copy of the altered gene from each parent. […] The way you inherit MSUD is what causes it to be more common in communities where people share similar genes (and similar genetic mutations).

• #7 Maple Syrup Urine Disease (MSUD) | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/maple-syrup-urine-disease-msud

  Maple syrup urine disease is a rare inherited disorder caused by the bodys inability to properly process amino acids, leading to a characteristic odor of maple syrup in the baby’s urine. […] Maple syrup urine disease is caused by mutations in one of three genes BCKDHA, BCKDHB or DBT. […] These genes provide instruction for the human body to make enzymes (BCKDH complex enzymes) which are essential for breaking down amino acids including leucine, isoleucine, and valine. […] Mutations to the three genes result in decreased or no activity of the enzymes. […] MSUD is inherited as an autosomal recessive pattern, meaning that both parents must carry the mutated gene to have a child with MSUD.

• #8

  https://www.omim.org/entry/248600

  A number sign (#) is used with this entry because maple syrup urine disease type IA (MSUD1A) is caused by homozygous or compound heterozygous mutation in the BCKDHA gene (608348), which encodes the E1-alpha subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), on chromosome 19q13. The BCKDC complex catalyzes the catabolism of the branched-chain amino acids, leucine, isoleucine, and valine. […] The major clinical features of maple syrup urine disease (MSUD) are mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids (BCAA) are present in the urine, resulting from a block in oxidative decarboxylation. There are 5 clinical subtypes of MSUD based on clinical presentation and biochemical response to thiamine administration: the classic neonatal severe form, an intermediate form, an intermittent form, a thiamine-responsive form, and an E3-deficient with lactic acidosis form (DLDD; 246900). All of these subtypes can be caused by mutation in the BCKDHA, BCKDHB, or DBT gene, except for the E3-deficient form, which is caused only by mutation in the DLD gene (Chuang and Shih, 2001).

• #9

  https://www.omim.org/entry/248600

  A number sign (#) is used with this entry because maple syrup urine disease type IA (MSUD1A) is caused by homozygous or compound heterozygous mutation in the BCKDHA gene (608348), which encodes the E1-alpha subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), on chromosome 19q13. The BCKDC complex catalyzes the catabolism of the branched-chain amino acids, leucine, isoleucine, and valine. […] The major clinical features of maple syrup urine disease (MSUD) are mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids (BCAA) are present in the urine, resulting from a block in oxidative decarboxylation. There are 5 clinical subtypes of MSUD based on clinical presentation and biochemical response to thiamine administration: the classic neonatal severe form, an intermediate form, an intermittent form, a thiamine-responsive form, and an E3-deficient with lactic acidosis form (DLDD; 246900). All of these subtypes can be caused by mutation in the BCKDHA, BCKDHB, or DBT gene, except for the E3-deficient form, which is caused only by mutation in the DLD gene (Chuang and Shih, 2001).

• #10

  https://www.omim.org/entry/248600

  A number sign (#) is used with this entry because maple syrup urine disease type IA (MSUD1A) is caused by homozygous or compound heterozygous mutation in the BCKDHA gene (608348), which encodes the E1-alpha subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), on chromosome 19q13. The BCKDC complex catalyzes the catabolism of the branched-chain amino acids, leucine, isoleucine, and valine. […] The major clinical features of maple syrup urine disease (MSUD) are mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids (BCAA) are present in the urine, resulting from a block in oxidative decarboxylation. There are 5 clinical subtypes of MSUD based on clinical presentation and biochemical response to thiamine administration: the classic neonatal severe form, an intermediate form, an intermittent form, a thiamine-responsive form, and an E3-deficient with lactic acidosis form (DLDD; 246900). All of these subtypes can be caused by mutation in the BCKDHA, BCKDHB, or DBT gene, except for the E3-deficient form, which is caused only by mutation in the DLD gene (Chuang and Shih, 2001).

• #11

  https://www.omim.org/entry/248600

  MSUD1B (620698) is caused by mutation in the BCKDHB gene (248611) on chromosome 6q14, and MSUD2 (620699) is caused by mutation in the DBT gene (248610) on chromosome 1p21. […] Mutation in the E3 component of the BCKDC complex, DLD (238331), on chromosome 7q31, causes an overlapping but more severe phenotype known as dihydrolipoamide dehydrogenase deficiency (DLDD; 246900). DLDD is sometimes referred to as MSUD3. […] In a patient with classic MSUD, Zhang et al. (1989, 1991) identified a mutation in the gene encoding the E1-alpha subunit (608348.0001). Chuang et al. (1994) later identified a second mutation in the BCKDHA gene in this patient (608348.0002). Each parent was heterozygous for 1 of the mutations. […] In 3 of 4 unrelated Hispanic-Mexican patients with intermediate MSUD, Chuang et al. (1995) identified a homozygous mutation in the BCKDHA gene (608348.0003). The fourth patient was homozygous for a different mutation in the BCKDHA gene (608348.0004). […] Patel and Harris (1995) provided a schematic representation of 7 point mutations, 1 small deletion, and 1 small insertion reported in the BCKDHA gene.

• #12 Overview of maple syrup urine disease – UpToDate

  https://www.uptodate.com/contents/overview-of-maple-syrup-urine-disease

  Maple syrup urine disease (MSUD; MIM #248600) also known as branched-chain ketoaciduria, is a disorder affecting the aliphatic or branched-chain amino acids (BCAAs). It is caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase complex (BCKDC), the second enzyme of the metabolic pathway of the three BCAAs, leucine, isoleucine, and valine. […] MSUD is caused by pathogenic variants of genes that encode branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) components E1-alpha, E1-beta, E2, and E3. […] The mode of inheritance is autosomal recessive. […] Homozygous or compound heterozygous variants in any of these genes can cause any of the forms of MSUD. […] There are case reports of a mild form of MSUD due to homozygous variants in the protein phosphatase, Mg2+/Mn2+ dependent 1K (PPM1K) gene encoding the BCKDC phosphatase. […] Pathogenic variants in the gene encoding the BCKDC kinase have not been identified. […] Decreased activity of BCKDC results in elevation of plasma concentrations of the BCAAs (leucine, isoleucine, and valine) and their corresponding keto acids.

• #13 Orphanet: Maple syrup urine disease

  https://www.orpha.net/en/disease/detail/511

  MSUD is due to mutations in the genes encoding subunits E1a, E1b, and E2 of the branched chain 2-ketoacid dehydrogenase (BCKAD) complex, involved in the second enzymatic step in the degradation of the branched chain amino acids (BCAAs): leucine, isoleucine and valine. […] Mutations in these genes lead to the accumulation of BCAAs (especially leucine) and their branched-chain alpha-ketoacids. […] A mutation in the PPM1K gene (4q22.1) has been reported in a single case of mild intermediate MSUD.

• #14 Maple syrup urine disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/maple-syrup-urine-disease/

  Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. […] Mutations in the BCKDHA, BCKDHB, and DBT genes can cause maple syrup urine disease. […] Mutations in any of these three genes reduce or eliminate the function of the protein complex, preventing the normal breakdown of leucine, isoleucine, and valine. […] Because high levels of these substances are toxic to the brain and other organs, their accumulation leads to the serious health problems associated with maple syrup urine disease.

• #15

  https://uihealthcare.adam.com/content.aspx?productid=117&pid=1&gid=000373

  Maple syrup urine disease (MSUD) is inherited, which means it is passed down through families. It is caused by a defect in 1 of 3 genes. People with this condition cannot break down the amino acids leucine, isoleucine, and valine. This leads to a buildup of these chemicals in the blood. […] In the most severe form, MSUD can damage the brain during times of physical stress (such as infection, fever, or not eating for a long time). […] Some types of MSUD are mild or come and go. Even in the mildest form, repeated periods of physical stress can cause intellectual disability and high levels of leucine to build up.

• #16 Maple syrup urine disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/maple-syrup-urine-disease/

  Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. […] Mutations in the BCKDHA, BCKDHB, and DBT genes can cause maple syrup urine disease. […] Mutations in any of these three genes reduce or eliminate the function of the protein complex, preventing the normal breakdown of leucine, isoleucine, and valine. […] Because high levels of these substances are toxic to the brain and other organs, their accumulation leads to the serious health problems associated with maple syrup urine disease.

• #17 Maple syrup urine disease – Wikipedia

  https://en.wikipedia.org/wiki/Maple_syrup_urine_disease

  Maple syrup urine disease (MSUD) is a rare, inherited metabolic disorder that affects the body’s ability to metabolize amino acids due to a deficiency in the activity of the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex. It particularly affects the metabolism of amino acids leucine, isoleucine, and valine. […] Mutations in the following genes cause maple syrup urine disease: BCKDHA, BCKDHB, DBT, and DLD. These four genes produce proteins that work together as the branched-chain alpha-keto acid dehydrogenase complex. The complex is essential for breaking down the amino acids leucine, isoleucine, and valine. […] Mutation in any of these genes reduces or eliminates the function of the enzyme complex, preventing the normal breakdown of isoleucine, leucine, and valine. As a result, these amino acids and their by-products build up in the body. Because high levels of these substances are toxic to the brain and other organs, this accumulation leads to the serious medical problems associated with maple syrup urine disease.

• #18 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Maple syrup urine disease is caused by defects in the branched-chain alpha-ketoacid dehydrogenase complex proteins. These are nuclear-encoded mitochondrial proteins. Mutations have been identified in four proteins of the complex: E1-alpha and E1-beta subunits composing the dimeric E1 or branched-chain alpha-ketoacid decarboxylase, the branched-chain dihydrolipoamide acyltransferase (E2), and lipoamide oxidoreductase (E3). […] Loading studies in maple syrup urine disease patients revealed that leucine (and alpha-isocaproate, leucines ketoacid present in equimolar concentration with leucine) increases were associated with the most severe neurologic symptoms, especially if levels were above 1 mM. […] A plethora of subsequent studies have suggested that the pathophysiology of maple syrup urine disease is complex. Research in the pathophysiology of maple syrup urine disease revolves around:

• #19 Maple Syrup Urine Disease (MSUD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946234-overview

  Maple syrup urine disease (MSUD), also known as branched-chain ketoaciduria, is an aminoacidopathy due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. […] The BCKD enzyme complex, which is associated with the inner mitochondrial membrane, has 3 different catalytic components (ie, E1, E2, E3) and 2 associated regulatory enzymes (ie, BCKD phosphatase, BCKD kinase). […] Mutations in E1, E2, or E3 cause maple syrup urine disease. […] No clear genotype-phenotype correlation between molecular and clinical phenotypes is known, with the exemption of mutations in E2, which cause thiamine-responsive maple syrup urine disease. […] Accumulation of plasma leucine causes neurological symptoms. […] The accumulation of plasma isoleucine is associated with the maple syrup urine odor.

• #20 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Inhibition of mitochondrial functions: […] Direct competition of branched-chain alpha-ketoacids for normal substrates of mitochondrial oxidative phosphorylation resulting in depleted pyruvate and ATP; […] AlphaKIC inhibits pyruvate dehydrogenase (PDH) leading to lactate accumulation (especially in the brain) and increased alanine […] AlphaKIC also inhibits alpha-ketoglutarate dehydrogenase (alphaKGDH) leading to accumulation of alphaKG, reduced Krebs cycle flux, and ATP depletion. […] Apoptosis induction […] Reactive oxygen species, both as a consequence of Krebs cycle inhibition and as mediators of respiratory chain inhibition. […] Competition of leucine with other large neutral amino acids for transport across the BBB, thus, reducing neurotransmitter synthesis, and also reducing cerebral protein synthesis.

• #21 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Inhibition of mitochondrial functions: […] Direct competition of branched-chain alpha-ketoacids for normal substrates of mitochondrial oxidative phosphorylation resulting in depleted pyruvate and ATP; […] AlphaKIC inhibits pyruvate dehydrogenase (PDH) leading to lactate accumulation (especially in the brain) and increased alanine […] AlphaKIC also inhibits alpha-ketoglutarate dehydrogenase (alphaKGDH) leading to accumulation of alphaKG, reduced Krebs cycle flux, and ATP depletion. […] Apoptosis induction […] Reactive oxygen species, both as a consequence of Krebs cycle inhibition and as mediators of respiratory chain inhibition. […] Competition of leucine with other large neutral amino acids for transport across the BBB, thus, reducing neurotransmitter synthesis, and also reducing cerebral protein synthesis.

• #22 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Inhibition of mitochondrial functions: […] Direct competition of branched-chain alpha-ketoacids for normal substrates of mitochondrial oxidative phosphorylation resulting in depleted pyruvate and ATP; […] AlphaKIC inhibits pyruvate dehydrogenase (PDH) leading to lactate accumulation (especially in the brain) and increased alanine […] AlphaKIC also inhibits alpha-ketoglutarate dehydrogenase (alphaKGDH) leading to accumulation of alphaKG, reduced Krebs cycle flux, and ATP depletion. […] Apoptosis induction […] Reactive oxygen species, both as a consequence of Krebs cycle inhibition and as mediators of respiratory chain inhibition. […] Competition of leucine with other large neutral amino acids for transport across the BBB, thus, reducing neurotransmitter synthesis, and also reducing cerebral protein synthesis.

• #23 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Inhibition of mitochondrial functions: […] Direct competition of branched-chain alpha-ketoacids for normal substrates of mitochondrial oxidative phosphorylation resulting in depleted pyruvate and ATP; […] AlphaKIC inhibits pyruvate dehydrogenase (PDH) leading to lactate accumulation (especially in the brain) and increased alanine […] AlphaKIC also inhibits alpha-ketoglutarate dehydrogenase (alphaKGDH) leading to accumulation of alphaKG, reduced Krebs cycle flux, and ATP depletion. […] Apoptosis induction […] Reactive oxygen species, both as a consequence of Krebs cycle inhibition and as mediators of respiratory chain inhibition. […] Competition of leucine with other large neutral amino acids for transport across the BBB, thus, reducing neurotransmitter synthesis, and also reducing cerebral protein synthesis.

• #24 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Inhibition of mitochondrial functions: […] Direct competition of branched-chain alpha-ketoacids for normal substrates of mitochondrial oxidative phosphorylation resulting in depleted pyruvate and ATP; […] AlphaKIC inhibits pyruvate dehydrogenase (PDH) leading to lactate accumulation (especially in the brain) and increased alanine […] AlphaKIC also inhibits alpha-ketoglutarate dehydrogenase (alphaKGDH) leading to accumulation of alphaKG, reduced Krebs cycle flux, and ATP depletion. […] Apoptosis induction […] Reactive oxygen species, both as a consequence of Krebs cycle inhibition and as mediators of respiratory chain inhibition. […] Competition of leucine with other large neutral amino acids for transport across the BBB, thus, reducing neurotransmitter synthesis, and also reducing cerebral protein synthesis.

• #25 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Inhibition of mitochondrial functions: […] Direct competition of branched-chain alpha-ketoacids for normal substrates of mitochondrial oxidative phosphorylation resulting in depleted pyruvate and ATP; […] AlphaKIC inhibits pyruvate dehydrogenase (PDH) leading to lactate accumulation (especially in the brain) and increased alanine […] AlphaKIC also inhibits alpha-ketoglutarate dehydrogenase (alphaKGDH) leading to accumulation of alphaKG, reduced Krebs cycle flux, and ATP depletion. […] Apoptosis induction […] Reactive oxygen species, both as a consequence of Krebs cycle inhibition and as mediators of respiratory chain inhibition. […] Competition of leucine with other large neutral amino acids for transport across the BBB, thus, reducing neurotransmitter synthesis, and also reducing cerebral protein synthesis.

• #26 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Interference with myelin synthesis, which could be secondary to decreased ketone production from BCAA. […] Decreased alpha-adrenergic and beta-adrenergic receptor binding in synaptosomes. […] Alterations of intermediate filament phosphorylation. […] Increased secretion of the neurotrophic cytokine S100B.

• #27 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Interference with myelin synthesis, which could be secondary to decreased ketone production from BCAA. […] Decreased alpha-adrenergic and beta-adrenergic receptor binding in synaptosomes. […] Alterations of intermediate filament phosphorylation. […] Increased secretion of the neurotrophic cytokine S100B.

• #28 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Interference with myelin synthesis, which could be secondary to decreased ketone production from BCAA. […] Decreased alpha-adrenergic and beta-adrenergic receptor binding in synaptosomes. […] Alterations of intermediate filament phosphorylation. […] Increased secretion of the neurotrophic cytokine S100B.

• #29 Maple syrup urine disease | MedLink Neurology

  https://www.medlink.com/articles/maple-syrup-urine-disease

  Interference with myelin synthesis, which could be secondary to decreased ketone production from BCAA. […] Decreased alpha-adrenergic and beta-adrenergic receptor binding in synaptosomes. […] Alterations of intermediate filament phosphorylation. […] Increased secretion of the neurotrophic cytokine S100B.

• #30 Overview of maple syrup urine disease – UpToDate

  https://www.uptodate.com/contents/overview-of-maple-syrup-urine-disease/print

  Maple syrup urine disease (MSUD; MIM #248600) also known as branched-chain ketoaciduria, is a disorder affecting the aliphatic or branched-chain amino acids (BCAAs). It is caused by a deficiency of branched-chain alpha-ketoacid dehydrogenase complex (BCKDC), the second enzyme of the metabolic pathway of the three BCAAs, leucine, isoleucine, and valine. […] MSUD is caused by pathogenic variants of genes that encode branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) components E1-alpha, E1-beta, E2, and E3. […] The mode of inheritance is autosomal recessive. […] Homozygous or compound heterozygous variants in any of these genes can cause any of the forms of MSUD. […] Elevated levels of BCAA interfere with normal function of the immune system, skeletal muscle, and central nervous system, exerting direct and indirect neurotoxic effects through tissue swelling, impaired glutamate homeostasis, and relative deficiency of large neutral amino acids, resulting in reduced neurotransmitter synthesis including dopamine and serotonin.

• #31 Symptoms of Maple Syrup Urine Disease: Life Expectancy, Causes

  https://www.medicinenet.com/what_are_the_symptoms_of_maple_syrup_urine_disease/article.htm

  Maple syrup urine disease (MSUD) is a rare genetic metabolic disorder that affects the way the body processes branched-chain amino acids (BCCAs), such as leucine, isoleucine, and valine. […] Six causes of maple syrup urine disease (MSUD) include the following: […] MSUD is caused by mutations in one of three genes that provide instructions for making the enzymes responsible for breaking down the branched-chain amino acids (BCAAs). […] In individuals with MSUD, the enzymes responsible for breaking down leucine, isoleucine, and valine are deficient or absent. […] MSUD symptoms can be triggered by consuming foods high in BCAAs, such as dairy products, meat, and certain grains. […] Stressful events, such as infections, surgery, or trauma, can also trigger MSUD symptoms by increasing the body’s demand for BCAAs. […] Poor compliance with treatment can lead to a buildup of these amino acids and their byproducts, which can cause symptoms and long-term complications. […] Some medications and supplements can contain BCAAs, increasing the risk of complications in individuals with MSUD.

• #32 Symptoms of Maple Syrup Urine Disease: Life Expectancy, Causes

  https://www.medicinenet.com/what_are_the_symptoms_of_maple_syrup_urine_disease/article.htm

  Maple syrup urine disease (MSUD) is a rare genetic metabolic disorder that affects the way the body processes branched-chain amino acids (BCCAs), such as leucine, isoleucine, and valine. […] Six causes of maple syrup urine disease (MSUD) include the following: […] MSUD is caused by mutations in one of three genes that provide instructions for making the enzymes responsible for breaking down the branched-chain amino acids (BCAAs). […] In individuals with MSUD, the enzymes responsible for breaking down leucine, isoleucine, and valine are deficient or absent. […] MSUD symptoms can be triggered by consuming foods high in BCAAs, such as dairy products, meat, and certain grains. […] Stressful events, such as infections, surgery, or trauma, can also trigger MSUD symptoms by increasing the body’s demand for BCAAs. […] Poor compliance with treatment can lead to a buildup of these amino acids and their byproducts, which can cause symptoms and long-term complications. […] Some medications and supplements can contain BCAAs, increasing the risk of complications in individuals with MSUD.

• #33 Symptoms of Maple Syrup Urine Disease: Life Expectancy, Causes

  https://www.medicinenet.com/what_are_the_symptoms_of_maple_syrup_urine_disease/article.htm

  Maple syrup urine disease (MSUD) is a rare genetic metabolic disorder that affects the way the body processes branched-chain amino acids (BCCAs), such as leucine, isoleucine, and valine. […] Six causes of maple syrup urine disease (MSUD) include the following: […] MSUD is caused by mutations in one of three genes that provide instructions for making the enzymes responsible for breaking down the branched-chain amino acids (BCAAs). […] In individuals with MSUD, the enzymes responsible for breaking down leucine, isoleucine, and valine are deficient or absent. […] MSUD symptoms can be triggered by consuming foods high in BCAAs, such as dairy products, meat, and certain grains. […] Stressful events, such as infections, surgery, or trauma, can also trigger MSUD symptoms by increasing the body’s demand for BCAAs. […] Poor compliance with treatment can lead to a buildup of these amino acids and their byproducts, which can cause symptoms and long-term complications. […] Some medications and supplements can contain BCAAs, increasing the risk of complications in individuals with MSUD.

• #34

  https://uihealthcare.adam.com/content.aspx?productid=117&pid=1&gid=000373

  Maple syrup urine disease (MSUD) is inherited, which means it is passed down through families. It is caused by a defect in 1 of 3 genes. People with this condition cannot break down the amino acids leucine, isoleucine, and valine. This leads to a buildup of these chemicals in the blood. […] In the most severe form, MSUD can damage the brain during times of physical stress (such as infection, fever, or not eating for a long time). […] Some types of MSUD are mild or come and go. Even in the mildest form, repeated periods of physical stress can cause intellectual disability and high levels of leucine to build up.

• #35 Symptoms of Maple Syrup Urine Disease: Life Expectancy, Causes

  https://www.medicinenet.com/what_are_the_symptoms_of_maple_syrup_urine_disease/article.htm

  Maple syrup urine disease (MSUD) is a rare genetic metabolic disorder that affects the way the body processes branched-chain amino acids (BCCAs), such as leucine, isoleucine, and valine. […] Six causes of maple syrup urine disease (MSUD) include the following: […] MSUD is caused by mutations in one of three genes that provide instructions for making the enzymes responsible for breaking down the branched-chain amino acids (BCAAs). […] In individuals with MSUD, the enzymes responsible for breaking down leucine, isoleucine, and valine are deficient or absent. […] MSUD symptoms can be triggered by consuming foods high in BCAAs, such as dairy products, meat, and certain grains. […] Stressful events, such as infections, surgery, or trauma, can also trigger MSUD symptoms by increasing the body’s demand for BCAAs. […] Poor compliance with treatment can lead to a buildup of these amino acids and their byproducts, which can cause symptoms and long-term complications. […] Some medications and supplements can contain BCAAs, increasing the risk of complications in individuals with MSUD.

• #36 Symptoms of Maple Syrup Urine Disease: Life Expectancy, Causes

  https://www.medicinenet.com/what_are_the_symptoms_of_maple_syrup_urine_disease/article.htm

  Maple syrup urine disease (MSUD) is a rare genetic metabolic disorder that affects the way the body processes branched-chain amino acids (BCCAs), such as leucine, isoleucine, and valine. […] Six causes of maple syrup urine disease (MSUD) include the following: […] MSUD is caused by mutations in one of three genes that provide instructions for making the enzymes responsible for breaking down the branched-chain amino acids (BCAAs). […] In individuals with MSUD, the enzymes responsible for breaking down leucine, isoleucine, and valine are deficient or absent. […] MSUD symptoms can be triggered by consuming foods high in BCAAs, such as dairy products, meat, and certain grains. […] Stressful events, such as infections, surgery, or trauma, can also trigger MSUD symptoms by increasing the body’s demand for BCAAs. […] Poor compliance with treatment can lead to a buildup of these amino acids and their byproducts, which can cause symptoms and long-term complications. […] Some medications and supplements can contain BCAAs, increasing the risk of complications in individuals with MSUD.

• #37

  https://uihealthcare.adam.com/content.aspx?productid=117&pid=1&gid=000373

  Maple syrup urine disease (MSUD) is inherited, which means it is passed down through families. It is caused by a defect in 1 of 3 genes. People with this condition cannot break down the amino acids leucine, isoleucine, and valine. This leads to a buildup of these chemicals in the blood. […] In the most severe form, MSUD can damage the brain during times of physical stress (such as infection, fever, or not eating for a long time). […] Some types of MSUD are mild or come and go. Even in the mildest form, repeated periods of physical stress can cause intellectual disability and high levels of leucine to build up.

• #38 Maple Syrup Urine Disease (MSUD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946234-overview

  Maple syrup urine disease occurs in about 1 case per 185,000 live births. […] As an autosomal recessive disorder, maple syrup urine disease is more prevalent in populations with a high occurrence of consanguinity. […] Infants with untreated early onset (ie, classic) maple syrup urine disease have significant developmental delay and die within the first months of life. […] All children are at increased risk for metabolic decompensation during periods of increased protein catabolism (eg, intercurrent illness, trauma, surgery).

• #39 Maple Syrup Urine Disease Models to be Presented in San Diego

  https://www.hcplive.com/view/hemoshear-msud-models

  MSUD is a rare genetic disorder caused by the deficiency of specific enzymes essential to metabolize proteins, leading to the speedy accumulation of life-threatening toxins in the body. […] Per the National Institute of Health (NIH), MSUD affects approximately 1 in 185,000 infants worldwide. This devastating disease causes lethargy, irritability and poor feeding, and results in developmental delays and brain damage. The condition is associated with a maple syrup odor in urine, sweat and earwax. Some symptoms can be controlled by strict dietary restrictions, however, there are currently no effective approved treatments for MSUD.

• #40 Maple Syrup Urine Disease (MSUD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946234-overview

  Maple syrup urine disease occurs in about 1 case per 185,000 live births. […] As an autosomal recessive disorder, maple syrup urine disease is more prevalent in populations with a high occurrence of consanguinity. […] Infants with untreated early onset (ie, classic) maple syrup urine disease have significant developmental delay and die within the first months of life. […] All children are at increased risk for metabolic decompensation during periods of increased protein catabolism (eg, intercurrent illness, trauma, surgery).

• #41 Bethel College – Mennonite Life

  https://mla.bethelks.edu/ml-archive/2015/maple-syrup-urine-disease-a-study-of-carrier-frequ.php

  Maple syrup urine disease is an autosomal recessive genetic disease which causes maple syrup urine odor, hypoglycemia, and a failure to catabolize leucine, isoleucine, and valine. […] MSUD occurs more often in Old Order Mennonite and Mennonite populations because of the smaller gene pools and higher rates of inbreeding. […] MSUD is caused by a mutation in the branched chain keto acid dehydrogenase E1 encoded by the alpha polypeptide gene. […] In the Mennonite population, however, the mutation is caused by an asparagine to tyrosine substitution. […] Due to the inbreeding of the Old Order Mennonite population, the frequency of homozygous genotypes increased and the rate of heterozygous genotypes decreased, which led to a higher incidence of the disease within the population. […] A carrier frequency of 4.17% for MSUD was found in the Mennonite population and a carrier frequency of 0% was found in the non-Mennonite population.

• #42 Bethel College – Mennonite Life

  https://mla.bethelks.edu/ml-archive/2015/maple-syrup-urine-disease-a-study-of-carrier-frequ.php

  The carrier frequency of MUSD is 4.17% in the Mennonite population whereas the known carrier frequency is 7.96% in Old Order Mennonite populations. […] The Mennonite population is likely to be less genetically isolated than Old Order Mennonite populations but more potentially genetically isolated than the non-Mennonites based on the differences in carrier frequency. […] Inbreeding increases the number of homozygous offspring, which increases the incidence of recessive disorders. […] The two participants in this study who are carriers would have no way of knowing they are carriers without having participated in the study. […] Outbreeding can greatly decrease the incidence of homozygous recessive diseases in the population.

• #43 Bethel College – Mennonite Life

  https://mla.bethelks.edu/ml-archive/2015/maple-syrup-urine-disease-a-study-of-carrier-frequ.php

  Maple syrup urine disease is an autosomal recessive genetic disease which causes maple syrup urine odor, hypoglycemia, and a failure to catabolize leucine, isoleucine, and valine. […] MSUD occurs more often in Old Order Mennonite and Mennonite populations because of the smaller gene pools and higher rates of inbreeding. […] MSUD is caused by a mutation in the branched chain keto acid dehydrogenase E1 encoded by the alpha polypeptide gene. […] In the Mennonite population, however, the mutation is caused by an asparagine to tyrosine substitution. […] Due to the inbreeding of the Old Order Mennonite population, the frequency of homozygous genotypes increased and the rate of heterozygous genotypes decreased, which led to a higher incidence of the disease within the population. […] A carrier frequency of 4.17% for MSUD was found in the Mennonite population and a carrier frequency of 0% was found in the non-Mennonite population.

• #44 Bethel College – Mennonite Life

  https://mla.bethelks.edu/ml-archive/2015/maple-syrup-urine-disease-a-study-of-carrier-frequ.php

  Maple syrup urine disease is an autosomal recessive genetic disease which causes maple syrup urine odor, hypoglycemia, and a failure to catabolize leucine, isoleucine, and valine. […] MSUD occurs more often in Old Order Mennonite and Mennonite populations because of the smaller gene pools and higher rates of inbreeding. […] MSUD is caused by a mutation in the branched chain keto acid dehydrogenase E1 encoded by the alpha polypeptide gene. […] In the Mennonite population, however, the mutation is caused by an asparagine to tyrosine substitution. […] Due to the inbreeding of the Old Order Mennonite population, the frequency of homozygous genotypes increased and the rate of heterozygous genotypes decreased, which led to a higher incidence of the disease within the population. […] A carrier frequency of 4.17% for MSUD was found in the Mennonite population and a carrier frequency of 0% was found in the non-Mennonite population.

• #45 Bethel College – Mennonite Life

  https://mla.bethelks.edu/ml-archive/2015/maple-syrup-urine-disease-a-study-of-carrier-frequ.php

  The carrier frequency of MUSD is 4.17% in the Mennonite population whereas the known carrier frequency is 7.96% in Old Order Mennonite populations. […] The Mennonite population is likely to be less genetically isolated than Old Order Mennonite populations but more potentially genetically isolated than the non-Mennonites based on the differences in carrier frequency. […] Inbreeding increases the number of homozygous offspring, which increases the incidence of recessive disorders. […] The two participants in this study who are carriers would have no way of knowing they are carriers without having participated in the study. […] Outbreeding can greatly decrease the incidence of homozygous recessive diseases in the population.

• #46

  https://www.omim.org/entry/248600

  A number sign (#) is used with this entry because maple syrup urine disease type IA (MSUD1A) is caused by homozygous or compound heterozygous mutation in the BCKDHA gene (608348), which encodes the E1-alpha subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), on chromosome 19q13. The BCKDC complex catalyzes the catabolism of the branched-chain amino acids, leucine, isoleucine, and valine. […] The major clinical features of maple syrup urine disease (MSUD) are mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids (BCAA) are present in the urine, resulting from a block in oxidative decarboxylation. There are 5 clinical subtypes of MSUD based on clinical presentation and biochemical response to thiamine administration: the classic neonatal severe form, an intermediate form, an intermittent form, a thiamine-responsive form, and an E3-deficient with lactic acidosis form (DLDD; 246900). All of these subtypes can be caused by mutation in the BCKDHA, BCKDHB, or DBT gene, except for the E3-deficient form, which is caused only by mutation in the DLD gene (Chuang and Shih, 2001).

• #47 Maple syrup urine disease (MSUD) | EBSCO Research Starters

  https://www.ebsco.com/research-starters/health-and-medicine/maple-syrup-urine-disease-msud

  Maple syrup urine disease (MSUD) is a rare genetic disorder caused by the deficiency or inactivity of a specific enzyme responsible for metabolizing branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine. […] This autosomal recessive condition leads to the accumulation of these amino acids and their toxic byproducts in the blood, particularly affecting brain function. […] The classic form of the disease results in little (less than 2 percent) or no BCKD activity. […] As a result of deficient branched-chain alpha-ketoacid dehydrogenase (BCKD), the essential branched chain amino acids leucine, isoleucine, and valine are not metabolized in patients with maple syrup urine disease (MSUD). […] High levels of leucine are especially toxic. […] If the disease is untreated, then intellectual and developmental disabilities, various neurological symptoms such as seizures, and even death can result. […] Because MSUD is caused by a recessive gene, there is a one in four chance that two heterozygous carriers will have an affected child.

• #48 Maple syrup urine disease type Ib | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/maple-syrup-urine-disease-type-ib/

  Individuals with intermediate MSUD have some BCKAD enzyme activity. […] This form of the disease is rare. In individuals with intermittent MSUD, BCKAD enzyme activity is reduced but not absent. […] Thiamine-responsive MSUD is distinct in that individuals with this form of the disease are expected to show a decrease in symptoms when treated with large doses of thiamine (vitamin B1). […] If untreated, MSUD can be fatal. […] It is particularly critical to recognize the disease as soon as symptoms appear in order to avoid brain damage and mental disability.

• #49 Maple syrup urine disease type Ib | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/maple-syrup-urine-disease-type-ib/

  Individuals with intermediate MSUD have some BCKAD enzyme activity. […] This form of the disease is rare. In individuals with intermittent MSUD, BCKAD enzyme activity is reduced but not absent. […] Thiamine-responsive MSUD is distinct in that individuals with this form of the disease are expected to show a decrease in symptoms when treated with large doses of thiamine (vitamin B1). […] If untreated, MSUD can be fatal. […] It is particularly critical to recognize the disease as soon as symptoms appear in order to avoid brain damage and mental disability.

• #50 Maple syrup urine disease type Ib | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/maple-syrup-urine-disease-type-ib/

  Individuals with intermediate MSUD have some BCKAD enzyme activity. […] This form of the disease is rare. In individuals with intermittent MSUD, BCKAD enzyme activity is reduced but not absent. […] Thiamine-responsive MSUD is distinct in that individuals with this form of the disease are expected to show a decrease in symptoms when treated with large doses of thiamine (vitamin B1). […] If untreated, MSUD can be fatal. […] It is particularly critical to recognize the disease as soon as symptoms appear in order to avoid brain damage and mental disability.

• #51

  https://www.omim.org/entry/248600

  A number sign (#) is used with this entry because maple syrup urine disease type IA (MSUD1A) is caused by homozygous or compound heterozygous mutation in the BCKDHA gene (608348), which encodes the E1-alpha subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), on chromosome 19q13. The BCKDC complex catalyzes the catabolism of the branched-chain amino acids, leucine, isoleucine, and valine. […] The major clinical features of maple syrup urine disease (MSUD) are mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids (BCAA) are present in the urine, resulting from a block in oxidative decarboxylation. There are 5 clinical subtypes of MSUD based on clinical presentation and biochemical response to thiamine administration: the classic neonatal severe form, an intermediate form, an intermittent form, a thiamine-responsive form, and an E3-deficient with lactic acidosis form (DLDD; 246900). All of these subtypes can be caused by mutation in the BCKDHA, BCKDHB, or DBT gene, except for the E3-deficient form, which is caused only by mutation in the DLD gene (Chuang and Shih, 2001).

• #52

  https://www.omim.org/entry/248600

  A number sign (#) is used with this entry because maple syrup urine disease type IA (MSUD1A) is caused by homozygous or compound heterozygous mutation in the BCKDHA gene (608348), which encodes the E1-alpha subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), on chromosome 19q13. The BCKDC complex catalyzes the catabolism of the branched-chain amino acids, leucine, isoleucine, and valine. […] The major clinical features of maple syrup urine disease (MSUD) are mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids (BCAA) are present in the urine, resulting from a block in oxidative decarboxylation. There are 5 clinical subtypes of MSUD based on clinical presentation and biochemical response to thiamine administration: the classic neonatal severe form, an intermediate form, an intermittent form, a thiamine-responsive form, and an E3-deficient with lactic acidosis form (DLDD; 246900). All of these subtypes can be caused by mutation in the BCKDHA, BCKDHB, or DBT gene, except for the E3-deficient form, which is caused only by mutation in the DLD gene (Chuang and Shih, 2001).

• #53 Maple Syrup Urine Disease (MSUD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946234-overview

  Maple syrup urine disease (MSUD), also known as branched-chain ketoaciduria, is an aminoacidopathy due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. […] The BCKD enzyme complex, which is associated with the inner mitochondrial membrane, has 3 different catalytic components (ie, E1, E2, E3) and 2 associated regulatory enzymes (ie, BCKD phosphatase, BCKD kinase). […] Mutations in E1, E2, or E3 cause maple syrup urine disease. […] No clear genotype-phenotype correlation between molecular and clinical phenotypes is known, with the exemption of mutations in E2, which cause thiamine-responsive maple syrup urine disease. […] Accumulation of plasma leucine causes neurological symptoms. […] The accumulation of plasma isoleucine is associated with the maple syrup urine odor.

• #54 Maple Syrup Urine Disease (MSUD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946234-overview

  Maple syrup urine disease occurs in about 1 case per 185,000 live births. […] As an autosomal recessive disorder, maple syrup urine disease is more prevalent in populations with a high occurrence of consanguinity. […] Infants with untreated early onset (ie, classic) maple syrup urine disease have significant developmental delay and die within the first months of life. […] All children are at increased risk for metabolic decompensation during periods of increased protein catabolism (eg, intercurrent illness, trauma, surgery).

• #55 Maple Syrup Urine Disease (MSUD)

  https://www.umassmed.edu/GrayEdwardsLab/research/maple-syrup-urine-disease-msud/

  Maple Syrup Urine Disease (MSUD) is a recessive metabolism disorder that causes severe neurological symptoms and causes fatal swelling of the brain in infants. This devastating disease is caused by a mutation in one of three genes, BCKDHA, BCKDHB and DBT, that forms a protein complex that breaks down large amino acids, branched-chain amino acids (BCAAs) essential for life. […] Due to mutations in one of these genes results in a dysfunctional protein that can no longer break down these BCAAs and thus causes toxic accumulation in cells throughout the body. […] If not diagnosed immediately at birth, children will develop highly fatal cerebral edema (brain swelling) and subsequent coma in just a few days. […] Liver transplantation is a potential therapeutic strategy for MSUD but has major disadvantages, such as shortage of available organs, high inherent risks, and it does not alleviate behavioral/cognitive deficits.

• #56 The Molecular Basis of Maple Syrup Urine Disease

  https://digitalcommons.liberty.edu/honors/1422/

  Maple syrup urine disease (MSUD) is a rare metabolic disorder that is caused by mutations in the branched chain alpha keto acid dehydrogenase enzyme complex (BCKDC). […] There are three main genes, the BCKDHA, BCKDHB, and DBT, that affect the BCKDC, all contributing to the onset of the disease. […] MSUD causes encephalopathy, neural deficits, maple syrup scented urine, coma, and even death if not treated due to the aggregation of branched-chain amino acids (BCAAs).

• #57 Neonatal gene therapy achieves sustained disease rescue of maple syrup urine disease in mice | Nature Communications

  https://www.nature.com/articles/s41467-022-30880-w

  Maple syrup urine disease (MSUD) is a rare recessively inherited metabolic disorder causing accumulation of branched chain amino acids leading to neonatal death, if untreated. […] This autosomal recessive disorder with an incidence of one in 185,000 live births is caused by a defective activity of the branched-chain 2-keto acid dehydrogenase (BCKD) enzyme leading to the accumulation of branched-chain amino acids (BCAA) leucine, isoleucine, valine and their corresponding 2-ketoacids (BCKA) in tissues and body fluids. […] MSUD is caused by mutations in BCKDHA, BCKDHB or DBT genes respectively coding for E1, E1, and E2 subunits and accounting for 45, 35, and 20% of MSUD patients, respectively. […] Neurotoxicity in MSUD is related to the accumulation of leucine and 2-ketoisocaproic acid (KIC, the ketoacid derived from leucine). […] In the classical severe form of MSUD (85-95% of cases), with less than 3% residual enzyme activity, this accumulation causes coma and cerebral edema shortly after birth with early death in the absence of aggressive and rapid management.

• #58 Maple syrup urine disease type Ib | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/maple-syrup-urine-disease-type-ib/

  Maple syrup urine disease (MSUD) type Ib, caused by mutations in the BCKDHB gene, is an inherited metabolic disorder named for the characteristic maple syrup odor of an affected individual’s urine. MSUD is caused by the lack of an enzyme needed to break down three amino acids (building blocks of proteins): leucine, isoleucine, and valine, which are collectively known as branched-chain amino acids. […] Without the needed enzyme, known as branched-chain ketoacid dehydrogenase (BCKAD) complex, these amino acids and their byproducts accumulate and cause damage to the body. […] The most common type, classic MSUD, is characterized by little or no BCKAD enzyme activity. […] Individuals with the disease are particularly prone to crisis during illness, during infection, during fasting, or after surgery.

• #59 The Molecular Basis of Maple Syrup Urine Disease

  https://digitalcommons.liberty.edu/honors/1422/

  Maple syrup urine disease (MSUD) is a rare metabolic disorder that is caused by mutations in the branched chain alpha keto acid dehydrogenase enzyme complex (BCKDC). […] There are three main genes, the BCKDHA, BCKDHB, and DBT, that affect the BCKDC, all contributing to the onset of the disease. […] MSUD causes encephalopathy, neural deficits, maple syrup scented urine, coma, and even death if not treated due to the aggregation of branched-chain amino acids (BCAAs).

• #60 Maple Syrup Urine Disease (MSUD): Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/946234-overview

  Maple syrup urine disease occurs in about 1 case per 185,000 live births. […] As an autosomal recessive disorder, maple syrup urine disease is more prevalent in populations with a high occurrence of consanguinity. […] Infants with untreated early onset (ie, classic) maple syrup urine disease have significant developmental delay and die within the first months of life. […] All children are at increased risk for metabolic decompensation during periods of increased protein catabolism (eg, intercurrent illness, trauma, surgery).

• #61

  https://uihealthcare.adam.com/content.aspx?productid=117&pid=1&gid=000373

  Maple syrup urine disease (MSUD) is inherited, which means it is passed down through families. It is caused by a defect in 1 of 3 genes. People with this condition cannot break down the amino acids leucine, isoleucine, and valine. This leads to a buildup of these chemicals in the blood. […] In the most severe form, MSUD can damage the brain during times of physical stress (such as infection, fever, or not eating for a long time). […] Some types of MSUD are mild or come and go. Even in the mildest form, repeated periods of physical stress can cause intellectual disability and high levels of leucine to build up.

• #62 Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

  https://www.mdpi.com/1422-0067/21/20/7490

  Overall, the dysregulation of these AAs may lead to brain dysfunction, predisposing MSUD patients to cognitive and psychiatric disabilities despite major clinical interventions such as liver transplant. […] Studies of neurological symptoms in MSUD patients remain somewhat limited. Currently, available literature showed that, despite strict diet therapy or liver transplantation that restore peripheral BCAA homeostasis, MSUD patients are at higher risk for neuropsychological impairments including cognitive deficits and mental illness (anxiety, depression, ADHD, and OCD) compared to healthy controls.

• #63 Newborn Screening Program – Maple Syrup Urine Disease

  http://www.idph.state.il.us/healthwellness/fs/msud.htm

  Maple syrup urine disease (MSUD) is an inherited disorder of amino acid metabolism, caused by a deficiency in an enzyme complex that results in defects in the catabolism of the amino acids leucine, isoleucine and valine. […] Deficiency of a component enzyme within this pathway causes accumulation of branched-chain amino acids and ketoacids in body fluids and tissues resulting in the clinical manifestations of MSUD.

• #64 Maple syrup urine disease | Handouts | MedLink Neurology

  https://www.medlink.com/handouts/maple-syrup-urine-disease

  Maple Syrup Urine Disease (MSUD) is a disorder in the body’s ability to use three of the essential amino acids in protein. […] In MSUD, the enzymes necessary to break down leucine, isoleucine and valine, are either absent, inactive, or only partially active. […] MSUD is a recessive genetic disease. This means both parents of a child with MSUD must carry a mutation in the same gene (the same genetic code). These mutated genes do not function normally, thus causing disease. […] When parents are both carriers of the gene for MSUD, with each pregnancy, there is a 1 in 4 chance of having a baby with MSUD, a 2 in 4 chance that the baby will have only one gene for MSUD and be a carrier like the parents, and a 1 in 4 chance that the baby will neither be a carrier nor have MSUD. […] Cerebral edema is a major concern in managing MSUD. Cerebral edema is the accumulation of excess fluid on the brain caused by an imbalance between electrolytes and the amino acids. […] With strict dietary compliance and good medical care, children with MSUD can, and do, lead relatively normal lives. […] Therapy must be started at the earliest possible age to achieve the best possible outcome.

• #65 Maple syrup urine disease | Handouts | MedLink Neurology

  https://www.medlink.com/handouts/maple-syrup-urine-disease

  Maple Syrup Urine Disease (MSUD) is a disorder in the body’s ability to use three of the essential amino acids in protein. […] In MSUD, the enzymes necessary to break down leucine, isoleucine and valine, are either absent, inactive, or only partially active. […] MSUD is a recessive genetic disease. This means both parents of a child with MSUD must carry a mutation in the same gene (the same genetic code). These mutated genes do not function normally, thus causing disease. […] When parents are both carriers of the gene for MSUD, with each pregnancy, there is a 1 in 4 chance of having a baby with MSUD, a 2 in 4 chance that the baby will have only one gene for MSUD and be a carrier like the parents, and a 1 in 4 chance that the baby will neither be a carrier nor have MSUD. […] Cerebral edema is a major concern in managing MSUD. Cerebral edema is the accumulation of excess fluid on the brain caused by an imbalance between electrolytes and the amino acids. […] With strict dietary compliance and good medical care, children with MSUD can, and do, lead relatively normal lives. […] Therapy must be started at the earliest possible age to achieve the best possible outcome.

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