Inborn errors of metabolism in a neonatology unit: Impact and long-term results

Inborn errors of metabolism (IEMs) are a group of inherited diseases with variable incidences. IEMs are caused by disrupting enzyme activities in specific metabolic pathways by genetic mutations, either directly or indirectly by cofactor deficiencies, causing altered levels of compounds associated with these pathways. While IEMs may present with multiple overlapping symptoms and metabolites, early and accurate diagnosis of IEMs is critical for the long-term health of affected subjects. The prevalence of IEMs differs between countries, likely because different IEM classifications and IEM screening methods are used. Currently, newborn screening programs exclusively use targeted metabolic assays that focus on limited panels of compounds for selected IEM diseases. Such targeted approaches face the problem of false negative and false positive diagnoses that could be overcome if metabolic screening adopted analyses of a broader range of analytes. Hence, we here review the prospects of using untargeted metabolomics for IEM screening. Untargeted metabolomics and lipidomics do not rely on predefined target lists and can detect as many metabolites as possible in a sample, allowing to screen for many metabolic pathways simultaneously. Examples are given for nontargeted analyses of IEMs, and prospects and limitations of different metabolomics methods are discussed. We conclude that dedicated studies are needed to compare accuracy and robustness of targeted and untargeted methods with respect to widening the scope of IEM diagnostics.

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Long-Term Stability of Amino Acids and Acylcarnitines in Dried Blood Spots

Clinical Chemistry ◽

10.1373/clinchem.2006.076679 ◽

2007 ◽

Vol 53 (4) ◽

pp. 717-722 ◽

Cited By ~ 54

Author(s):

Kristina Anna Strnadová ◽

Margareta Holub ◽

Adolf Mühl ◽

Georg Heinze ◽

Rene Ratschmann ◽

...

Keyword(s):

Amino Acids ◽

Inborn Errors Of Metabolism ◽

Dried Blood Spots ◽

Inborn Errors ◽

Retrospective Diagnosis ◽

Term Stability ◽

Long Term Stability ◽

Blood Filter ◽

Long Chain

Abstract Background: Dried blood filter cards, collected for newborn screening, are often stored for long periods of time. They may be suitable for the retrospective diagnosis of inborn errors of metabolism, but no data are currently available on the long-term stability of amino acids and acylcarnitine species. Methods: We analyzed amino acids and acylcarnitines by tandem mass spectrometry in 660 anonymous, randomly selected filter cards from 1989 through 2004. We assessed long-term stability of metabolites by linear regression and estimated annual decrease of concentration for each metabolite. Results: Concentrations of free carnitine increased by 7.6% per year during the first 5 years of storage and decreased by 1.4% per year thereafter. Alanine, arginine, leucine, methionine, and phenylalanine decreased by 6.5%, 3.3%, 3.1%, 7.3%, and 5.7% per year, respectively. Acetylcarnitine, propionylcarnitine, citrulline, glycine, and ornithine decreased by 18.5%, 27.4%, 8.1%, 14.7%, and 16.3% per year during the first 5 years, respectively; thereafter the decline was more gradual. Tyrosine decreased by 1.7% per year during the first 5 years and 7.9% per year thereafter. We could not analyze medium- and long-chain acylcarnitine species because of low physiological concentrations. Conclusions: Estimation of the annual decrease of metabolites may allow for the retrospective diagnosis of inborn errors of metabolism in filter cards that have been stored for long periods of time.

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Long-term effects of bone marrow transplantation for inborn errors of metabolism: A study of four patients with lysosomal storage diseases

Pediatrics International ◽

10.1111/j.1442-200x.1994.tb03125.x ◽

1994 ◽

Vol 36 (1) ◽

pp. 30-36 ◽

Cited By ~ 36

Author(s):

MASUE IMAIZUMI ◽

KAZUO GUSHI ◽

IKUO KUROBANE ◽

SHIGEO INOUE ◽

JUN SUZUKI ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Inborn Errors Of Metabolism ◽

Lysosomal Storage Diseases ◽

Lysosomal Storage ◽

Long Term Effects ◽

Inborn Errors ◽

Storage Diseases

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Bone-Marrow and Fetal-Liver Transplantation in Immunodeficiencies and Inborn Errors of Metabolism: Lack of Significant Restriction of T-Cell Function in Long-Term Chimeras Despite HLA-Mismatch

Immunological Reviews ◽

10.1111/j.1600-065x.1983.tb01070.x ◽

1983 ◽

Vol 71 (1) ◽

pp. 103-121 ◽

Cited By ~ 36

Author(s):

Jean-Louis Touraine

Keyword(s):

Bone Marrow ◽

Liver Transplantation ◽

T Cell ◽

Inborn Errors Of Metabolism ◽

Cell Function ◽

Fetal Liver ◽

Inborn Errors ◽

T Cell Function

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Neurometabolic Disorders Associated With Disturbances of Small Molecule Metabolism

10.1093/med/9780197512166.003.0120 ◽

2021 ◽

pp. 1092-1105

Author(s):

Deborah L. Renaud

Keyword(s):

Small Molecule ◽

Inborn Errors Of Metabolism ◽

Clinical Symptoms ◽

Inborn Errors ◽

Biochemical Processes ◽

Live Births ◽

Biochemical Pathways ◽

Neurometabolic Disorders ◽

Acute Exacerbations

Inborn errors of metabolism affect approximately 1 in 1,000 to 1 in 3,000 live births. Most of these inherited conditions are autosomal recessive, although a few are autosomal dominant or X-linked. Mitochondrial DNA disorders may be maternally inherited. The clinical symptoms associated with inborn errors of metabolism reflect the disruption of normal biochemical processes required for synthesis, breakdown, or transport of metabolites. This impairment leads to accumulation of metabolites that cause toxic effects, inadequate levels of metabolites required for normal cellular activity, or secondary disruption of essential metabolic pathways. Small molecule disorders involve the metabolism of amino acids, organic acids, carbohydrates, fatty acids, and other biochemical pathways. These disorders may present with acute exacerbations superimposed on long-term neurologic symptoms.

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