Materiały źródłowe

• #1 Genetic Metabolic Disorder Test: Detect Inherited Metabolic Disease

  https://diagnostics.medgenome.com/metabolic-genetics/

  Metabolic diseases span a vast range of conditions. Inherited metabolic disorders have a defective gene that results in an enzyme deficiency. […] Most metabolic disorders are genetic in origin. While metabolic disorders are individually rare, collectively they affect 1% to 3% of the world population. […] Early diagnosis of metabolic disorders can lead to better cost-effective management of disease conditions. […] Most genetic metabolic disorders have no specific clinical appearances, and their clinical manifestations are highly complex and variable. […] Individuals presenting with the symptoms of metabolic disorders. […] Actia offers a broad range of pre-designed gene mutation panels which have been developed with an in-depth understanding of genetic disorders by incorporating the latest research in this domain.

• #2 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. […] This group encompasses many metabolic disorders which are identifiable through standard metabolic assessments, such as amino acids and organic acids analysis, and are often responsive to dietary interventions. […] Disorders affecting carbohydrate metabolism represent a diverse group of conditions with varying clinical presentations. […] These disorders can be categorised based on either deficiencies or hyperactivity of specific enzymes involved in carbohydrate metabolism.

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

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

  It is absolutely essential that doctors diagnose IMDs early and whenever necessary, refer the patient to a tertiary care centre for better care, detailed laboratory workup, and management. […] Recognition of IMDs is important as it is quite common in incidence. […] Early diagnosis is important, as in most cases, dietary restriction and early therapy prevents onset of disability. […] In view of the nonspecific nature of clinical manifestations of IMDs, laboratory-based diagnosis often has a major role in confirmation or otherwise to rule out the suspected case of IMD. […] Confirmed diagnosis based on laboratory investigations helps in early medical intervention. […] Through proper diagnosis and treatment, it is possible to prevent the natural history of the disease. […] The increasing application of new technologies, such as electrospray ionisation tandem mass spectrometry, to newborn screening in asymptomatic persons allows earlier identification of IMDs. […] Accurate diagnosis is important for medical management, determining prognosis and genetic counselling.

• #4 Inherited metabolic disorders – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/inherited-metabolic-disorders/diagnosis-treatment/drc-20561225

  Some inherited metabolic disorders may be diagnosed before birth. Others can be diagnosed by routine newborn screening tests done at birth. Others are identified only after a child or adult shows symptoms of a disorder. […] To find out if you or your child has an inherited metabolic disorder, you may have: […] Genetic testing can identify the type of inherited metabolic disorder you or your child has. If one person in the family has an inherited metabolic disorder, specialists often recommend genetic testing and counseling for other family members as well. […] In some cases, future parents may choose to have carrier testing before pregnancy, also called preconception screening. This test can identify some gene changes in parents that may increase the risk that future children will have certain types of inherited metabolic disorders.

• #5 Inherited metabolic disorders – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/inherited-metabolic-disorders/diagnosis-treatment/drc-20561225

  Some inherited metabolic disorders may be diagnosed before birth. Others can be diagnosed by routine newborn screening tests done at birth. Others are identified only after a child or adult shows symptoms of a disorder. […] To find out if you or your child has an inherited metabolic disorder, you may have: […] Genetic testing can identify the type of inherited metabolic disorder you or your child has. If one person in the family has an inherited metabolic disorder, specialists often recommend genetic testing and counseling for other family members as well. […] In some cases, future parents may choose to have carrier testing before pregnancy, also called preconception screening. This test can identify some gene changes in parents that may increase the risk that future children will have certain types of inherited metabolic disorders.

• #6 Diagnosis and Treatment of Inherited Metabolic Disorders – Pediatric Neurology and Neurosurgery | NewYork-Presbyterian

  https://www.nyp.org/pediatrics/neurology-and-neurosurgery/inherited-metabolic-disorders/diagnosis-and-treatment

  Many inherited metabolic disorders can be found during pregnancy, which enables you to plan your baby’s care before delivery and know what your baby will need after they are born. […] Within 48 hours of birth, all babies are screened for 40 inborn errors of metabolism genetic defects that interfere with their ability to process substances like carbohydrates, proteins, and fats. Newborns with positive screening test results for these inherited metabolic disorders are referred to our Inherited Metabolic Disease Specialty Center for additional testing, clinical follow-up, and care if the diagnosis of a metabolic disorder is confirmed. […] If your child has a diagnosis of a metabolic disorder, our multidisciplinary team of specialists provide treatment specific to each patient’s metabolic condition.

• #7 Diagnosis and Treatment of Inherited Metabolic Disorders – Pediatric Neurology and Neurosurgery | NewYork-Presbyterian

  https://www.nyp.org/pediatrics/neurology-and-neurosurgery/inherited-metabolic-disorders/diagnosis-and-treatment

  Many inherited metabolic disorders can be found during pregnancy, which enables you to plan your baby’s care before delivery and know what your baby will need after they are born. […] Within 48 hours of birth, all babies are screened for 40 inborn errors of metabolism genetic defects that interfere with their ability to process substances like carbohydrates, proteins, and fats. Newborns with positive screening test results for these inherited metabolic disorders are referred to our Inherited Metabolic Disease Specialty Center for additional testing, clinical follow-up, and care if the diagnosis of a metabolic disorder is confirmed. […] If your child has a diagnosis of a metabolic disorder, our multidisciplinary team of specialists provide treatment specific to each patient’s metabolic condition.

• #8 Laboratory diagnostic approaches in metabolic disorders

  https://atm.amegroups.org/article/view/22705/html

  The diagnosis of inborn errors of metabolism (IEM) takes many forms. […] Due to the implementation and advances in newborn screening (NBS), the diagnosis of many IEM has become relatively easy utilizing laboratory biomarkers. […] However, due to molecular, biochemical, and clinical variability of IEM, not all disorders included in NBS programs will be detected and diagnosed by screening alone. […] This article provides a general overview and simplified guidelines for the diagnosis of IEM in patients with and without an acute metabolic decompensation, with early or late onset of clinical symptoms. […] The proper use of routine laboratory results in the initial patient assessment is also discussed, which can help guide efficient ordering of specialized laboratory tests to confirm a potential diagnosis and initiate treatment as soon as possible.

• #9 Diagnosis and Treatment of Inherited Metabolic Disorders – Pediatric Neurology and Neurosurgery | NewYork-Presbyterian

  https://www.nyp.org/pediatrics/neurology-and-neurosurgery/inherited-metabolic-disorders/diagnosis-and-treatment

  Many inherited metabolic disorders can be found during pregnancy, which enables you to plan your baby’s care before delivery and know what your baby will need after they are born. […] Within 48 hours of birth, all babies are screened for 40 inborn errors of metabolism genetic defects that interfere with their ability to process substances like carbohydrates, proteins, and fats. Newborns with positive screening test results for these inherited metabolic disorders are referred to our Inherited Metabolic Disease Specialty Center for additional testing, clinical follow-up, and care if the diagnosis of a metabolic disorder is confirmed. […] If your child has a diagnosis of a metabolic disorder, our multidisciplinary team of specialists provide treatment specific to each patient’s metabolic condition.

• #10 allworth Diagnostics – allworth Diagnostics

  https://allworthdiagnostics.com/

  Inherited Metabolic Disorders are a group of medical conditions where an underlying genetic change impacts the bodys ability to breakdown everyday food constituents. […] Diagnosis of the most prevalent Inherited Metabolic Disorders usually occurs in the first few days of life through national screening programs based on the well known heel prick test. Once diagnosed, clinical management for Inherited Metabolic Disorders is life long and is typically based on dietary management, supplementation and often pharmaceutical therapy. […] Allworth Diagnostics products are monitoring tools, providing the Inherited Metabolic Disorder community with a real time solution to regularly monitor these critical metabolite levels in their blood from the convenience of their home. […] The current methodology for blood phenylalanine monitoring is based on patients self-collecting dried blood spot samples and mailing them to a centralised laboratory for analysis on a large central lab system.

• #11 Metabolomic Diagnostic in Inherited Metabolic Disorders: Historical Progress and Future Perspectives | IntechOpen

  https://www.intechopen.com/chapters/1198080

  It is important to emphasize the significance of introducing quality management systems in diagnostic laboratories through the incorporation of ISO standards. […] The evolution of different chromatographic and mass spectrometry techniques throughout the history of inherited metabolic diseases diagnosis. […] The implementation of chromatography with tandem mass spectrometry (MS/MS) was a turning point in the detection of IMD, as it allowed for the detection of many metabolites from different metabolic pathways. […] Thus, early years of the 21st century have served to establish multiple methods using HPLC or UPLC-MS/MS for the analysis of multiple targeted metabolites for the diagnosis and treatment monitoring of various IMD. […] In recent years, with this technology, there has been a growing trend to analyze broader panels of metabolites in a single sample, but it presents limitations in terms of the number of metabolites, and they must always be previously known.

• #12 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. […] Inherited metabolic disorders are present at birth, and some are detected by routine screening. All 50 states screen newborns for phenylketonuria. Most states also test newborns for galactosemia. But no state tests babies for all known inherited metabolic disorders. […] Improved testing technology has led many states to expand newborn screening for genetic metabolic disorders. The National Newborn Screening and Genetics Resources Center provides information on each states screening practices. […] Once symptoms develop, specific blood or DNA tests are available to diagnose most genetic metabolic disorders. Being referred to a specialized center (usually at a university) increases your chances of a correct diagnosis. […] But as Tise points out, these disorders are often thought of as affecting children, so they may not be on your doctors list of possible suspects if you dont show symptoms until adulthood.

• #13 Laboratory diagnostic approaches in metabolic disorders

  https://atm.amegroups.org/article/view/22705/html

  Although the classical presentation of most IEM involves an acutely ill newborn or young infant, this scenario is encountered less frequently now that advances in tandem mass-spectrometry-based NBS have decreased the number of acute episodes and consequent sequelae for many of the conditions identified by the screening test. […] However, because patients with milder mutations and subtle biochemical phenotypes may be missed by the cut-off values used to determine positive screening results, a normal newborn screen should not exclude these disorders from the differential diagnosis in a patient whose clinical presentation is suggestive of an inherited metabolic defect. […] Basic laboratory tests are still important and often provide the first clues to a possible underlying IEM. […] The first step in helping to select the appropriate laboratory investigation to rule out an IEM is to determine whether the condition is likely due to defects in small molecule metabolism or defects of organelle metabolism.

• #14 Inherited metabolic disorders – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/inherited-metabolic-disorders/diagnosis-treatment/drc-20561225

  Some inherited metabolic disorders may be diagnosed before birth. Others can be diagnosed by routine newborn screening tests done at birth. Others are identified only after a child or adult shows symptoms of a disorder. […] To find out if you or your child has an inherited metabolic disorder, you may have: […] Genetic testing can identify the type of inherited metabolic disorder you or your child has. If one person in the family has an inherited metabolic disorder, specialists often recommend genetic testing and counseling for other family members as well. […] In some cases, future parents may choose to have carrier testing before pregnancy, also called preconception screening. This test can identify some gene changes in parents that may increase the risk that future children will have certain types of inherited metabolic disorders.

• #15 Metabolic disorders

  https://www.rch.org.au/clinicalguide/guideline_index/metabolic_disorders/

  Metabolic disorders present at all ages with a variety of symptoms and signs that mimic common childhood illness. A high index of suspicion is needed to make a diagnosis […] Consider a metabolic disorder in any newborn with unexplained encephalopathy or progressive illness, particularly following an uncomplicated pregnancy and birth […] Once suspected, consult the metabolic team urgently […] Collection of appropriate urine and blood samples during an acute illness is the key to diagnosis, but should not delay management […] Metabolic disorders are a large group of inherited conditions resulting from a block (partial or complete) to a pathway in the body’s metabolism, or defects in the transport of substances […] Diagnosis and management should always involve close liaison with a metabolic team

• #16 An approach to the diagnosis of inherited metabolic disease | ADC Education & Practice Edition

  https://ep.bmj.com/content/95/2/40.short

  Inherited metabolic diseases (IMDs) pose a particular challenge to diagnosis. […] It is important to make IMD diagnoses because there are many effective treatments and early diagnosis greatly enhances the chance of a better outcome. […] Presentations are also non-specific further increasing the chances of a diagnosis being missed. […] It is therefore essential to develop an approach to thinking about and investigating IMDs, particularly when one considers that these patients will present initially to the local hospital rather than to the specialist centre.

• #17 Examination methods of inherited metabolic disorders – WikiLectures

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

  The available laboratory tests have different sensitivities due to the nature of the laboratory method and analyte. […] The output is a comprehensive picture of results that are difficult to interpret and require specialization. […] The reason for performing laboratory tests at the genetic, enzymatic and metabolite level is obtained by the doctor especially if: Hereditary disorders are indicated by a family history – consanguinity, similar manifestations in relatives, unexplained deaths in the family. […] The disease considered normal does not respond to the usual treatment. […] The disease is multi-systemic. […] Unexplained deviations from routine laboratory tests are found. […] Manifested manifestations of the disease are rare and at the same time typical for IMD – odor, urine color, specific dysmorphia (gargoilism), etc.

• #18 Examination methods of inherited metabolic disorders – WikiLectures

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

  The available laboratory tests have different sensitivities due to the nature of the laboratory method and analyte. […] The output is a comprehensive picture of results that are difficult to interpret and require specialization. […] The reason for performing laboratory tests at the genetic, enzymatic and metabolite level is obtained by the doctor especially if: Hereditary disorders are indicated by a family history – consanguinity, similar manifestations in relatives, unexplained deaths in the family. […] The disease considered normal does not respond to the usual treatment. […] The disease is multi-systemic. […] Unexplained deviations from routine laboratory tests are found. […] Manifested manifestations of the disease are rare and at the same time typical for IMD – odor, urine color, specific dysmorphia (gargoilism), etc.

• #19 Laboratory diagnostic approaches in metabolic disorders

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6331366/

  Appropriate and prudent test selection must be driven by a combination of the patients clinical presentation and the results of routine first tier laboratory tests, which can help guide more specific testing. […] Although biochemical genetic and molecular genetic tests are required to confirm a diagnosis, basic laboratory tests are still important and often provide the first clues to a possible underlying IEM. Medical and family history, clinical symptoms, and basic labs are usually adequate to categorize an IEM and provide initial treatment before the results of more specific testing are available, especially in an emergency situation. […] Based on the patients clinical presentation and the outcome of routine laboratory analyses, once the suspicion of a metabolic disorder has been established, the most informative subsequent testing will depend on the potential disorder or group of disorders included in the differential diagnosis. Laboratory tests that cast a wide net and can be used to diagnose multiple IEMs include urine organic acid, plasma and urine amino acid, plasma acylcarnitine, and serum very long chain fatty acid analyses.

• #20 Laboratory diagnostic approaches in metabolic disorders

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6331366/

  Appropriate and prudent test selection must be driven by a combination of the patients clinical presentation and the results of routine first tier laboratory tests, which can help guide more specific testing. […] Although biochemical genetic and molecular genetic tests are required to confirm a diagnosis, basic laboratory tests are still important and often provide the first clues to a possible underlying IEM. Medical and family history, clinical symptoms, and basic labs are usually adequate to categorize an IEM and provide initial treatment before the results of more specific testing are available, especially in an emergency situation. […] Based on the patients clinical presentation and the outcome of routine laboratory analyses, once the suspicion of a metabolic disorder has been established, the most informative subsequent testing will depend on the potential disorder or group of disorders included in the differential diagnosis. Laboratory tests that cast a wide net and can be used to diagnose multiple IEMs include urine organic acid, plasma and urine amino acid, plasma acylcarnitine, and serum very long chain fatty acid analyses.

• #21 Laboratory diagnostic approaches in metabolic disorders

  https://atm.amegroups.org/article/view/22705/html

  Patients with small molecule disorders usually present with acute illness requiring emergency intervention. […] Patients with disorders of organelle metabolism commonly present with neurological and neuromuscular manifestations, organomegaly, hepatic dysfunction, with or without dysmorphism. […] It is important to keep in mind that in some instances, disorders affecting organelle function may also present with metabolic crises including hypoglycemia and/or metabolic acidosis requiring emergency intervention. […] Basic laboratory tests should be performed in every child with an acute illness in whom an underlying metabolic disorder is a possibility. […] The following tests are examples of basic but nevertheless critical investigations to be considered when evaluating a patient for a potential IEM, as results can be directly affected by these disorders.

• #22 Laboratory diagnostic approaches in metabolic disorders

  https://atm.amegroups.org/article/view/22705/html

  Patients with small molecule disorders usually present with acute illness requiring emergency intervention. […] Patients with disorders of organelle metabolism commonly present with neurological and neuromuscular manifestations, organomegaly, hepatic dysfunction, with or without dysmorphism. […] It is important to keep in mind that in some instances, disorders affecting organelle function may also present with metabolic crises including hypoglycemia and/or metabolic acidosis requiring emergency intervention. […] Basic laboratory tests should be performed in every child with an acute illness in whom an underlying metabolic disorder is a possibility. […] The following tests are examples of basic but nevertheless critical investigations to be considered when evaluating a patient for a potential IEM, as results can be directly affected by these disorders.

• #23 Laboratory diagnostic approaches in metabolic disorders

  https://atm.amegroups.org/article/view/22705/html

  Determining the acid-base status is important in the assessment of a patient with a potential inherited metabolic defect, because high anion gap metabolic acidosis is usually caused by the accumulation of organic acids including lactic acid, ketone bodies, or unusual acids and their derivatives. […] The majority of IEM that present with overwhelming metabolic acidosis and ketosis are organic acidemias. […] Although some organic acidemias and disorders of mitochondrial fatty acid oxidation may also cause hyperammonemia, it is usually less significant. […] Urea cycle disorders are inherited deficiencies in any of the enzymes of the urea cycle, or in the production of the allosteric cofactor N-acetylglutamine, resulting in severe primary hyperammonemia. […] Once a non-metabolic etiology of hyperlactatemia has been ruled out, the most common origins of hyperlactatemia secondary to mitochondrial energy disruption by toxic metabolites are fatty acid oxidation disorders, organic acidurias, and in very rare cases, urea cycle defects.

• #24 Metabolic disorders

  https://www.rch.org.au/clinicalguide/guideline_index/metabolic_disorders/

  Metabolites indicative of metabolic disorders are best detected at time of acute presentation […] Careful collection and handling of blood, urine and CSF samples is important, but should not delay management of the unwell child […] Interpretation must take account of the clinical context – unwell children without an underlying metabolic disorder frequently have deranged blood gas values […] Consult the metabolic team urgently to discuss abnormal results […] Early consultation with metabolic team as soon as a metabolic disorder is suspected […] Interpretation of initial investigations serves as a guide only: consult the metabolic team with abnormal results.

• #25 Laboratory diagnostic approaches in metabolic disorders

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6331366/

  Appropriate and prudent test selection must be driven by a combination of the patients clinical presentation and the results of routine first tier laboratory tests, which can help guide more specific testing. […] Although biochemical genetic and molecular genetic tests are required to confirm a diagnosis, basic laboratory tests are still important and often provide the first clues to a possible underlying IEM. Medical and family history, clinical symptoms, and basic labs are usually adequate to categorize an IEM and provide initial treatment before the results of more specific testing are available, especially in an emergency situation. […] Based on the patients clinical presentation and the outcome of routine laboratory analyses, once the suspicion of a metabolic disorder has been established, the most informative subsequent testing will depend on the potential disorder or group of disorders included in the differential diagnosis. Laboratory tests that cast a wide net and can be used to diagnose multiple IEMs include urine organic acid, plasma and urine amino acid, plasma acylcarnitine, and serum very long chain fatty acid analyses.

• #26 Laboratory diagnostic approaches in metabolic disorders

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6331366/

  Appropriate and prudent test selection must be driven by a combination of the patients clinical presentation and the results of routine first tier laboratory tests, which can help guide more specific testing. […] Although biochemical genetic and molecular genetic tests are required to confirm a diagnosis, basic laboratory tests are still important and often provide the first clues to a possible underlying IEM. Medical and family history, clinical symptoms, and basic labs are usually adequate to categorize an IEM and provide initial treatment before the results of more specific testing are available, especially in an emergency situation. […] Based on the patients clinical presentation and the outcome of routine laboratory analyses, once the suspicion of a metabolic disorder has been established, the most informative subsequent testing will depend on the potential disorder or group of disorders included in the differential diagnosis. Laboratory tests that cast a wide net and can be used to diagnose multiple IEMs include urine organic acid, plasma and urine amino acid, plasma acylcarnitine, and serum very long chain fatty acid analyses.

• #27 Laboratory diagnostic approaches in metabolic disorders

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6331366/

  Appropriate and prudent test selection must be driven by a combination of the patients clinical presentation and the results of routine first tier laboratory tests, which can help guide more specific testing. […] Although biochemical genetic and molecular genetic tests are required to confirm a diagnosis, basic laboratory tests are still important and often provide the first clues to a possible underlying IEM. Medical and family history, clinical symptoms, and basic labs are usually adequate to categorize an IEM and provide initial treatment before the results of more specific testing are available, especially in an emergency situation. […] Based on the patients clinical presentation and the outcome of routine laboratory analyses, once the suspicion of a metabolic disorder has been established, the most informative subsequent testing will depend on the potential disorder or group of disorders included in the differential diagnosis. Laboratory tests that cast a wide net and can be used to diagnose multiple IEMs include urine organic acid, plasma and urine amino acid, plasma acylcarnitine, and serum very long chain fatty acid analyses.

• #28 Metabolic Disorder Panel Diagnostics – Medical Laboratory | ARCHIMEDlife

  https://www.archimedlife.com/metabolic-disorder-diagnostics-enzyme-biomarker-genetics/

  Our complete catalog of laboratory diagnostic services support physicians by helping detect Rare Diseases fast. […] The diagnostic testing process includes pre-testing using biochemical assays for fast and reliable results, including biomarkers, where available (e.g. Lyso-GL-3 for Fabry). […] In most cases, testing is fast and easy using Dried Blood Spot (DBS) cards. This simple and minimally invasive technique supplies enough sample for biochemical testing and typically genetic confirmation testing as well. […] Our tests and diagnostic panels for Metabolic disorders typically include an enzymatic pre-test targeting enzyme deficiency and additional biomarker testing where available. In cases of positive or conspicuous pre-test results, genetic molecular analysis can be included. […] All of our services are available to any interested physician or healthcare professional worldwide.

• #29 Metabolic disorders

  https://www.rch.org.au/clinicalguide/guideline_index/metabolic_disorders/

  Metabolites indicative of metabolic disorders are best detected at time of acute presentation […] Careful collection and handling of blood, urine and CSF samples is important, but should not delay management of the unwell child […] Interpretation must take account of the clinical context – unwell children without an underlying metabolic disorder frequently have deranged blood gas values […] Consult the metabolic team urgently to discuss abnormal results […] Early consultation with metabolic team as soon as a metabolic disorder is suspected […] Interpretation of initial investigations serves as a guide only: consult the metabolic team with abnormal results.

• #30 Metabolic disorders

  https://www.rch.org.au/clinicalguide/guideline_index/metabolic_disorders/

  Metabolites indicative of metabolic disorders are best detected at time of acute presentation […] Careful collection and handling of blood, urine and CSF samples is important, but should not delay management of the unwell child […] Interpretation must take account of the clinical context – unwell children without an underlying metabolic disorder frequently have deranged blood gas values […] Consult the metabolic team urgently to discuss abnormal results […] Early consultation with metabolic team as soon as a metabolic disorder is suspected […] Interpretation of initial investigations serves as a guide only: consult the metabolic team with abnormal results.

• #31 Laboratory diagnostic approaches in metabolic disorders

  https://atm.amegroups.org/article/view/22705/html

  In cases where a patient finally, in spite of the reduction in morbidity and mortality following the implementation of widespread NBS, improvements in therapy, and the identification of later-onset clinical presentation of most IEM, it is inevitable that some patients will pass away before a diagnosis is made. […] In these instances, it is important to collect post mortem blood and urine specimens whenever possible, to aid in identifying any underlying metabolic disorder.

• #32 Genetic Diagnosis in a Cohort of Adult Patients with Inherited Metabolic Diseases: A Single-Center Experience

  https://www.mdpi.com/2218-273X/12/7/920

  Inherited metabolic diseases (IMDs) are genetic conditions that result in metabolism alterations. […] Although research-based Next Generation Sequencing (NGS) testing for IMD has been recently implemented, its application in a clinical diagnostic setting remains challenging. […] Genetic testing plays a major role in the management of adult subjects with an IMD as it not only increases the accuracy of diagnosis, but also allows for family members testing and genetic counseling prior to procreation. […] The recent implementation of research-based Next Generation Sequencing (NGS) testing for IMDs has, in part, overcome these difficulties and it is no longer cost prohibitive to use NGS to understand the genetics of each single patient. […] However, NGS application to IMDs in a clinical diagnostic setting remains challenging.

• #33 A review of multiple diagnostic approaches in the undiagnosed diseases network to identify inherited metabolic diseases | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03423-3

  Currently, the detection of rare and undiagnosed genetic disorders is improved by next generation sequencing (NGS) methodologies, which includes exome (ES) and genome sequencing (GS). In the same vein, NGS has significant promise for clinical utility in diagnosing IMD. […] We demonstrated in Table 2 that a wide variety of diagnostic methods were needed to evaluate and diagnose an IMD in UDN subjects, including ES/GS, biochemical phenotyping, clinical phenotyping, CMA, vitro/vivo studies, mitochondrial DNA sequencing, gene panels, single gene tests, and RNA sequencing. […] While UDN ES had powerful diagnostic utility as described in Table 2 and seven cases (Table 3), it may miss diagnoses. […] It is also important to be aware that NGS serves as an indispensable yet incomplete tool for achieving a definitive diagnosis of IMD. While NGS whether ES/GS, can provide critical information to diagnose IMDs, additional biochemical tests are often needed to confirm the diagnosis.

• #34 Metabolic Disorders – CENTOGENE

  https://www.centogene.com/diagnostics/clinical-areas/metabolic-disorders/

  Whole Exome Sequencing (WES) enables quicker and cost-effective diagnosis for patients with complex and unclear symptoms. […] Multiomics give a deeper understanding of human biological processes and acts as a unique and highly effective tool for early diagnosis. […] Create a diagnostic gene panel by selecting genes tailored to individual patient needs.

• #35 Metabolic Disorders – CENTOGENE

  https://www.centogene.com/diagnostics/clinical-areas/metabolic-disorders/

  Whole Exome Sequencing (WES) enables quicker and cost-effective diagnosis for patients with complex and unclear symptoms. […] Multiomics give a deeper understanding of human biological processes and acts as a unique and highly effective tool for early diagnosis. […] Create a diagnostic gene panel by selecting genes tailored to individual patient needs.

• #36 Genetic Diagnosis in a Cohort of Adult Patients with Inherited Metabolic Diseases: A Single-Center Experience

  https://www.mdpi.com/2218-273X/12/7/920

  Inherited metabolic diseases (IMDs) are genetic conditions that result in metabolism alterations. […] Although research-based Next Generation Sequencing (NGS) testing for IMD has been recently implemented, its application in a clinical diagnostic setting remains challenging. […] Genetic testing plays a major role in the management of adult subjects with an IMD as it not only increases the accuracy of diagnosis, but also allows for family members testing and genetic counseling prior to procreation. […] The recent implementation of research-based Next Generation Sequencing (NGS) testing for IMDs has, in part, overcome these difficulties and it is no longer cost prohibitive to use NGS to understand the genetics of each single patient. […] However, NGS application to IMDs in a clinical diagnostic setting remains challenging.

• #37 A review of multiple diagnostic approaches in the undiagnosed diseases network to identify inherited metabolic diseases | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03423-3

  Currently, the detection of rare and undiagnosed genetic disorders is improved by next generation sequencing (NGS) methodologies, which includes exome (ES) and genome sequencing (GS). In the same vein, NGS has significant promise for clinical utility in diagnosing IMD. […] We demonstrated in Table 2 that a wide variety of diagnostic methods were needed to evaluate and diagnose an IMD in UDN subjects, including ES/GS, biochemical phenotyping, clinical phenotyping, CMA, vitro/vivo studies, mitochondrial DNA sequencing, gene panels, single gene tests, and RNA sequencing. […] While UDN ES had powerful diagnostic utility as described in Table 2 and seven cases (Table 3), it may miss diagnoses. […] It is also important to be aware that NGS serves as an indispensable yet incomplete tool for achieving a definitive diagnosis of IMD. While NGS whether ES/GS, can provide critical information to diagnose IMDs, additional biochemical tests are often needed to confirm the diagnosis.

• #38 P279: Application of next-generation sequencing in the diagnosis of inherited metabolic disorders in Iran: An 11-year overview | Twist Bioscience

  https://www.twistbioscience.com/resources/publication/p279-application-next-generation-sequencing-diagnosis-inherited-metabolic?utm_marketing_tactic=4020

  P279: Application of next-generation sequencing in the diagnosis of inherited metabolic disorders in Iran: An 11-year overview […] Inherited metabolic disorders (IMD), a diverse group of disorders with biochemical pathways alterations, are individually rare but collectively common in more than 1:800 individuals. […] Next-generation sequencing (NGS) technology enables the simultaneous sequencing of numerous genes with high precision and reliability. […] Variants in metabolic genes were detected in (622/3502, 17.7%) individuals subjected to NGS testing, ranging from prenatal to adulthood. […] According to the International Classification of Inherited Metabolic Disorders (ICIMD) group classification, the most commonly diagnosed groups of IMDs using the NGS technique were disorders of intermediary metabolism (136/384, 35.4%) and disorders of complex molecule and organelle metabolism (128/384, 33.3%), followed by the lipid metabolism and transport disorders at (32/384, 8.3%).

• #39 P279: Application of next-generation sequencing in the diagnosis of inherited metabolic disorders in Iran: An 11-year overview | Twist Bioscience

  https://www.twistbioscience.com/resources/publication/p279-application-next-generation-sequencing-diagnosis-inherited-metabolic?utm_marketing_tactic=4020

  P279: Application of next-generation sequencing in the diagnosis of inherited metabolic disorders in Iran: An 11-year overview […] Inherited metabolic disorders (IMD), a diverse group of disorders with biochemical pathways alterations, are individually rare but collectively common in more than 1:800 individuals. […] Next-generation sequencing (NGS) technology enables the simultaneous sequencing of numerous genes with high precision and reliability. […] Variants in metabolic genes were detected in (622/3502, 17.7%) individuals subjected to NGS testing, ranging from prenatal to adulthood. […] According to the International Classification of Inherited Metabolic Disorders (ICIMD) group classification, the most commonly diagnosed groups of IMDs using the NGS technique were disorders of intermediary metabolism (136/384, 35.4%) and disorders of complex molecule and organelle metabolism (128/384, 33.3%), followed by the lipid metabolism and transport disorders at (32/384, 8.3%).

• #40 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 develop when children inherit defective genes that control metabolism. […] Usually, a hereditary metabolic disorder is diagnosed by using a blood test or examination of a tissue sample to determine whether a specific enzyme is deficient or missing. Genetic testing is also sometimes used. […] After birth, many of these disorders are detected by routine newborn screening tests. […] Doctors may suspect a hereditary disorder of metabolism during a physical examination. Symptoms may provide clues as well.

• #41 Inherited metabolic disorders associated with hypoglycaemia in adulthood: a narrative review – Dawson – Journal of Laboratory and Precision Medicine

  https://jlpm.amegroups.org/article/view/6373/html

  An algorithm for recalling the IMD causes of fasting and post-prandial hypoglycaemia is shown in Figure 2. […] The key to the diagnosis is recognition of the association of symptoms with ingestion of fructose-containing foods and a positive effect from withdrawal of these foods from the diet. […] Confirmation of the diagnosis may be sought from mutation analysis of the ALDOB gene though occasionally a liver biopsy for enzyme activity is necessary.

• #42 Metabolic Disorder Panel Diagnostics – Medical Laboratory | ARCHIMEDlife

  https://www.archimedlife.com/metabolic-disorder-diagnostics-enzyme-biomarker-genetics/

  Our complete catalog of laboratory diagnostic services support physicians by helping detect Rare Diseases fast. […] The diagnostic testing process includes pre-testing using biochemical assays for fast and reliable results, including biomarkers, where available (e.g. Lyso-GL-3 for Fabry). […] In most cases, testing is fast and easy using Dried Blood Spot (DBS) cards. This simple and minimally invasive technique supplies enough sample for biochemical testing and typically genetic confirmation testing as well. […] Our tests and diagnostic panels for Metabolic disorders typically include an enzymatic pre-test targeting enzyme deficiency and additional biomarker testing where available. In cases of positive or conspicuous pre-test results, genetic molecular analysis can be included. […] All of our services are available to any interested physician or healthcare professional worldwide.

• #43 Extending inherited metabolic disorder diagnostics with biomarker interaction visualizations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10131334/

  Inherited Metabolic Disorders (IMDs) are rare diseases where one impaired protein leads to a cascade of changes in the adjacent chemical conversions. […] IMDs often present with non-specific symptoms, a lack of a clear genotype-phenotype correlation, and de novo mutations, complicating diagnosis. […] A timely and accurate diagnosis of IMDs, currently based on both symptoms and biomarkers measured in various bodily fluids, is required to initiate therapies, which are sparsely available. […] The current diagnostic process starts with a metabolic pediatrician, who based on the phenotype of a patient can request biochemical analyses on a patient sample (e.g. blood, urine). […] Methods to detect genetic variants (WES) are useful for the diagnosis of specific classes of IMDs where few or no specific metabolic biomarkers exist (e.g. mitochondrial disorders).

• #44 An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients | European Journal of Human Genetics

  https://www.nature.com/articles/s41431-022-01119-5

  To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). […] We show that integrated genetic and biochemical testing facilitated the decision on clinical relevance of the variants and led to a high diagnostic yield (37%), which is comparable to exome/genome sequencing. […] This multiomic approach constitutes a unique and highly effective tool for the genetic diagnosis of IMDs. […] In order to diagnose IMDs comprehensively, we have implemented a next generation sequencing (NGS) panel with over 200 genes that integrates genetic and biochemical testing performed in the same laboratory. This approach allows the efficient diagnosis of more than 180 metabolic diseases.

• #45 An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients | European Journal of Human Genetics

  https://www.nature.com/articles/s41431-022-01119-5

  To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). […] We show that integrated genetic and biochemical testing facilitated the decision on clinical relevance of the variants and led to a high diagnostic yield (37%), which is comparable to exome/genome sequencing. […] This multiomic approach constitutes a unique and highly effective tool for the genetic diagnosis of IMDs. […] In order to diagnose IMDs comprehensively, we have implemented a next generation sequencing (NGS) panel with over 200 genes that integrates genetic and biochemical testing performed in the same laboratory. This approach allows the efficient diagnosis of more than 180 metabolic diseases.

• #46 An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients | European Journal of Human Genetics

  https://www.nature.com/articles/s41431-022-01119-5

  To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). […] We show that integrated genetic and biochemical testing facilitated the decision on clinical relevance of the variants and led to a high diagnostic yield (37%), which is comparable to exome/genome sequencing. […] This multiomic approach constitutes a unique and highly effective tool for the genetic diagnosis of IMDs. […] In order to diagnose IMDs comprehensively, we have implemented a next generation sequencing (NGS) panel with over 200 genes that integrates genetic and biochemical testing performed in the same laboratory. This approach allows the efficient diagnosis of more than 180 metabolic diseases.

• #47 An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients | European Journal of Human Genetics

  https://www.nature.com/articles/s41431-022-01119-5

  To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). […] We show that integrated genetic and biochemical testing facilitated the decision on clinical relevance of the variants and led to a high diagnostic yield (37%), which is comparable to exome/genome sequencing. […] This multiomic approach constitutes a unique and highly effective tool for the genetic diagnosis of IMDs. […] In order to diagnose IMDs comprehensively, we have implemented a next generation sequencing (NGS) panel with over 200 genes that integrates genetic and biochemical testing performed in the same laboratory. This approach allows the efficient diagnosis of more than 180 metabolic diseases.

• #48 Metabolomic Diagnostic in Inherited Metabolic Disorders: Historical Progress and Future Perspectives | IntechOpen

  https://www.intechopen.com/chapters/1198080

  However, with the incorporation of high-resolution mass spectrometry (HRMS) these limitations can be overcome, as it is possible to analyze thousands of metabolites in a single sample and in a single analysis that do not have to be predefined. […] The analysis of data obtained by this technology can be managed in a targeted or non-targeted manner, offering seemingly infinite possibilities not only to discover new biomarkers or diseases but also to apply in diagnostics, ushering in a new era of next-generation metabolic screening. […] For decades, targeted metabolomics methods have been widely and successfully used for the diagnosis and monitoring of patients with IMD. […] However, these methods are more clinician-dependent, and clinical symptomatology typically guides the selection of specific analyses for an individual patient.

• #49 Metabolomic Diagnostic in Inherited Metabolic Disorders: Historical Progress and Future Perspectives | IntechOpen

  https://www.intechopen.com/chapters/1198080

  However, with the incorporation of high-resolution mass spectrometry (HRMS) these limitations can be overcome, as it is possible to analyze thousands of metabolites in a single sample and in a single analysis that do not have to be predefined. […] The analysis of data obtained by this technology can be managed in a targeted or non-targeted manner, offering seemingly infinite possibilities not only to discover new biomarkers or diseases but also to apply in diagnostics, ushering in a new era of next-generation metabolic screening. […] For decades, targeted metabolomics methods have been widely and successfully used for the diagnosis and monitoring of patients with IMD. […] However, these methods are more clinician-dependent, and clinical symptomatology typically guides the selection of specific analyses for an individual patient.

• #50 Extending inherited metabolic disorder diagnostics with biomarker interaction visualizations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10131334/

  Unfortunately, diagnosing IMDs using metabolites can be challenging due to the commonly observed overlap between biomarkers, since the individual compounds are often involved in more than one metabolic pathway and can therefore be metabolized to various products. […] The framework could aid in the diagnostic process of other (novel) IMDs and is adaptable to analyze different types of IMDs and functional assays in the future, as well as integrating other types of (omics) data analysis, e.g. transcriptomics, metabolomics, and fluxomics. […] The developed framework enables the visualization of clinical biomarker profiles with biological pathway knowledge, by connecting individual markers to changes on the process level. […] This approach shows which metabolic reactions are disturbed, which proteins are related to these reactions, and potentially which specific protein is impaired, aiding diagnosis.

• #51 Extending inherited metabolic disorder diagnostics with biomarker interaction visualizations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10131334/

  Unfortunately, diagnosing IMDs using metabolites can be challenging due to the commonly observed overlap between biomarkers, since the individual compounds are often involved in more than one metabolic pathway and can therefore be metabolized to various products. […] The framework could aid in the diagnostic process of other (novel) IMDs and is adaptable to analyze different types of IMDs and functional assays in the future, as well as integrating other types of (omics) data analysis, e.g. transcriptomics, metabolomics, and fluxomics. […] The developed framework enables the visualization of clinical biomarker profiles with biological pathway knowledge, by connecting individual markers to changes on the process level. […] This approach shows which metabolic reactions are disturbed, which proteins are related to these reactions, and potentially which specific protein is impaired, aiding diagnosis.

• #52 Extending inherited metabolic disorder diagnostics with biomarker interaction visualizations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10131334/

  Unfortunately, diagnosing IMDs using metabolites can be challenging due to the commonly observed overlap between biomarkers, since the individual compounds are often involved in more than one metabolic pathway and can therefore be metabolized to various products. […] The framework could aid in the diagnostic process of other (novel) IMDs and is adaptable to analyze different types of IMDs and functional assays in the future, as well as integrating other types of (omics) data analysis, e.g. transcriptomics, metabolomics, and fluxomics. […] The developed framework enables the visualization of clinical biomarker profiles with biological pathway knowledge, by connecting individual markers to changes on the process level. […] This approach shows which metabolic reactions are disturbed, which proteins are related to these reactions, and potentially which specific protein is impaired, aiding diagnosis.

• #53 Extending inherited metabolic disorder diagnostics with biomarker interaction visualizations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10131334/

  The developed framework is extendable with in-house biomarker data, knowledge from other databases or literature, and additional data from blood samples or other relevant matrices. […] The framework also leaves room for manual selection of potentially relevant pathways by experts, which could be aided by reviewing the patient-specific heatmap which visualizes theoretical biomarkers. […] In this study, the network model helped to easily diagnose 9 out of 16 patient samples and pointed in the correct direction or suggested follow-up analysis for 4 patients.

• #54 Extending inherited metabolic disorder diagnostics with biomarker interaction visualizations

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10131334/

  Inherited Metabolic Disorders (IMDs) are rare diseases where one impaired protein leads to a cascade of changes in the adjacent chemical conversions. […] IMDs often present with non-specific symptoms, a lack of a clear genotype-phenotype correlation, and de novo mutations, complicating diagnosis. […] A timely and accurate diagnosis of IMDs, currently based on both symptoms and biomarkers measured in various bodily fluids, is required to initiate therapies, which are sparsely available. […] The current diagnostic process starts with a metabolic pediatrician, who based on the phenotype of a patient can request biochemical analyses on a patient sample (e.g. blood, urine). […] Methods to detect genetic variants (WES) are useful for the diagnosis of specific classes of IMDs where few or no specific metabolic biomarkers exist (e.g. mitochondrial disorders).

• #55 Metabolic Clinic | Children’s Hospital Colorado

  https://www.childrenscolorado.org/doctors-and-departments/departments/genetics/metabolic/

  The Inherited Metabolic Diseases (IMD) Clinic consists of a multidisciplinary team dedicated to providing family focused care to children and adults with known or suspected inborn errors of metabolism. The clinic is recognized internationally for its expertise relative to diagnosis and treatment of metabolic disorders. It is the only clinic in the Rocky Mountain Region providing comprehensive metabolic services. […] The clinic provides diagnostic evaluations and therapeutic management of individuals of all ages in whom a metabolic disorder is diagnosed or considered. Early diagnosis and treatment of inborn errors of metabolism may help prevent developmental delays, organ damage, and, in some cases, death. […] The IMD Clinic staff evaluates patients for whom concern regarding an inborn error of metabolism has been raised. The evaluation process includes review of clinical and laboratory findings, plus family history information. Recommendations for additional evaluation are provided.

• #56 Metabolic disorders

  https://www.rch.org.au/clinicalguide/guideline_index/metabolic_disorders/

  Metabolites indicative of metabolic disorders are best detected at time of acute presentation […] Careful collection and handling of blood, urine and CSF samples is important, but should not delay management of the unwell child […] Interpretation must take account of the clinical context – unwell children without an underlying metabolic disorder frequently have deranged blood gas values […] Consult the metabolic team urgently to discuss abnormal results […] Early consultation with metabolic team as soon as a metabolic disorder is suspected […] Interpretation of initial investigations serves as a guide only: consult the metabolic team with abnormal results.

• #57 Metabolic disorders

  https://www.rch.org.au/clinicalguide/guideline_index/metabolic_disorders/

  Metabolites indicative of metabolic disorders are best detected at time of acute presentation […] Careful collection and handling of blood, urine and CSF samples is important, but should not delay management of the unwell child […] Interpretation must take account of the clinical context – unwell children without an underlying metabolic disorder frequently have deranged blood gas values […] Consult the metabolic team urgently to discuss abnormal results […] Early consultation with metabolic team as soon as a metabolic disorder is suspected […] Interpretation of initial investigations serves as a guide only: consult the metabolic team with abnormal results.

• #58 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. […] Improvements in medical technology and greater knowledge of the human genome are resulting in significant changes in the diagnosis, classification, and treatment of inherited metabolic disorders (IMDs). […] It is important that physicians recognise the clinical signs of IMDs and know when to propose advanced laboratory testing or referral to a higher centre for better patient management. […] Definitive diagnosis and management of patients with IMDs is ideally carried out by a combination of specialists, including an ophthalmologist, paediatrician, biochemist, and medical geneticist. […] 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.

• #59 A review of multiple diagnostic approaches in the undiagnosed diseases network to identify inherited metabolic diseases | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03423-3

  In summary, our UDN data show that the spectrum of IMDs detected in the UDN cohort is large and growing. This was due to the availability through the UDN of more current, robust, and sensitive methods at minimal cost to UDN participants. We hypothesize that the adoption of these and future methods to clinical practice promises to expand the spectrum of known IMDs that will improve diagnosis and treatment that may lead to additional clinical trials. Furthermore, we conclude combinations of multiple diagnostic approaches are required to detect IMDs that are presently missed by the traditional laboratory screening methods.

• #60 Diagnostics | Special Issue : Diagnosis, Biomarkers, and Treatment of Metabolic Disorders

  https://www.mdpi.com/journal/diagnostics/special_issues/920692E2X8

  Diagnosis, Biomarkers, and Treatment of Metabolic Disorders is a Special Issue published in the Journal Diagnostics (ISSN 2075-4418) which is an international scholarly open-access journal. It publishes original research articles and comprehensive reviews, and there is no restriction on the maximum length of the papers. Our aim is to encourage healthcare professionals and scientists to publish their experimental, theoretical, and original research related to any aspects of metabolic diseases in humans or animal models in as much detail as possible. Full experimental and/or methodological details must be provided for research articles. This includes clinical, experimental, genetic, biochemical, methodological, theoretical, ethical, and counseling aspects. […] The scope of this Special Issue includes as follows: […] Diagnosis of metabolic diseases; […] Inherited metabolic diseases; […] Artificial intelligence and machine learning in inherited metabolic diseases; […] Please visit the Instructions for Authors page before submitting a manuscript.

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