Inborn Errors of Metabolism

Vernon, Hilary J.

doi:10.1001/jamapediatrics.2015.0754

Cited by 104 publications

(37 citation statements)

References 39 publications

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“…The field is also expending to the more exploratory platforms such as a whole-genome sequencing and untargeted metabolomics. Although these modalities have some restrictions in clinical settings [1,49], they facilitate novel genes identification, novel biomarkers discovery and disease associations and thus strongly advancing the field [50,51].…”

Section: Author Detailsmentioning

confidence: 99%

Amino Acids Profiling for the Diagnosis of Metabolic Disorders

Sandlers¹

2020

Biochemical Testing - Clinical Correlation and Diagnosis

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Inborn errors of metabolism (IEM) represent a group of inherited diseases in which genetic defect leads to the block on a metabolic pathway, resulting in a single enzyme dysfunction. As a downstream consequence of the residual or full loss of the enzymatic activity, there is an accumulation of toxic metabolites in the proximity of the metabolic block and/or a deficiency of an essential metabolic product which leads to the clinical presentation of the disease. While individually IEMs are rare, a collectively estimated incidence of metabolic inherited disorders is 1:800. The genetic basis of IEMs can involve abnormalities such as point mutations, deletions or insertions, or more complex genomic rearrangements. Categorization of IEM can be simply made on the basis of the affected metabolic network: fatty acids oxidation disorders, protein/amino acids metabolism disorders, disorders of carbohydrate metabolism, lysosomal storage diseases, peroxisomal disorders, and mitochondrial diseases. This chapter will overview amino acid metabolism-related inherited disorders and amino acid analysis for the diagnosis and routine monitoring of this category of IEMs.

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Section: Author Detailsmentioning

confidence: 99%

Amino Acids Profiling for the Diagnosis of Metabolic Disorders

Sandlers¹

2020

Biochemical Testing - Clinical Correlation and Diagnosis

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“…However, if IEMs are recognized by early screening, many can be controlled with life-saving nutritional supplements and dietary interventions. Using current metabolite profiling platforms, which can now survey thousands of metabolites in microliter quantities of neonatal blood, we anticipate an enormously expanded scope of IEM diagnosis and the discovery of previously unrecognized genetic diseases in the near-term (Schulze et al 2003; Vernon 2015; Yoon 2015). …”

Section: Introductionmentioning

confidence: 99%

Metabolomics enables precision medicine: “A White Paper, Community Perspective”

et al. 2016

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Introduction: Background to metabolomicsMetabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or “-omics” level is a rapidly growing field that has the potential to have a profound impact upon medical practice. At the center of metabolomics, is the concept that a person’s metabolic state provides a close representation of that individual’s overall health status. This metabolic state reflects what has been encoded by the genome, and modified by diet, environmental factors, and the gut microbiome. The metabolic profile provides a quantifiable readout of biochemical state from normal physiology to diverse pathophysiologies in a manner that is often not obvious from gene expression analyses. Today, clinicians capture only a very small part of the information contained in the metabolome, as they routinely measure only a narrow set of blood chemistry analytes to assess health and disease states. Examples include measuring glucose to monitor diabetes, measuring cholesterol and high density lipoprotein/low density lipoprotein ratio to assess cardiovascular health, BUN and creatinine for renal disorders, and measuring a panel of metabolites to diagnose potential inborn errors of metabolism in neonates.Objectives of White Paper—expected treatment outcomes and metabolomics enabling tool for precision medicineWe anticipate that the narrow range of chemical analyses in current use by the medical community today will be replaced in the future by analyses that reveal a far more comprehensive metabolic signature. This signature is expected to describe global biochemical aberrations that reflect patterns of variance in states of wellness, more accurately describe specific diseases and their progression, and greatly aid in differential diagnosis. Such future metabolic signatures will: (1) provide predictive, prognostic, diagnostic, and surrogate markers of diverse disease states; (2) inform on underlying molecular mechanisms of diseases; (3) allow for sub-classification of diseases, and stratification of patients based on metabolic pathways impacted; (4) reveal biomarkers for drug response phenotypes, providing an effective means to predict variation in a subject’s response to treatment (pharmacometabolomics); (5) define a metabotype for each specific genotype, offering a functional read-out for genetic variants: (6) provide a means to monitor response and recurrence of diseases, such as cancers: (7) describe the molecular landscape in human performance applications and extreme environments. Importantly, sophisticated metabolomic analytical platforms and informatics tools have recently been developed that make it possible to measure thousands of metabolites in blood, other body fluids, and tissues. Such tools also enable more robust analysis of response to treatment. New insights have been gained about mechanisms of diseases, including neuropsychiatric disorders, cardiovascular disease, cancers...

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“…Left untreated, these disorders may be fatal, cause developmental delay or irreversibly decrease the quality of life, impair functionality, and affect overall lifespan. 2 Advances in technology and knowledge have substantially improved the prognosis of many IEMs; particularly the development and implementation of newborn screening (NBS) programs around the world. 3 NBS programs are population-based and aim to detect conditions in asymptomatic newborns where specific treatment or management can improve the disease outcome.…”

Section: Introductionmentioning

confidence: 99%

Inborn errors of metabolism in newcomer and refugee populations in Ontario, CA

Gannavarapu

Prasad²,

Prasad³

2019

UWOMJ

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Inborn errors of metabolism (IEM) are a heterogenous group of rare, inherited disorders that impair the biochemical processes involved in metabolism. Many are treated with various restrictive diets in early infancy, prior to the appearance of symptoms to improve the overall outcomes of the affected individuals. Identification of individuals at a risk of developing metabolic disorders through newborn screening (NBS) programs and the subsequent early diagnosis and treatment are an invaluable aspect of healthcare in Canada. Incorporation of Canada’s expanding population of refugees and new immigrants presents with potential challenges and changes. Without the availability of NBS programs in many countries contributing to the refugee influx in Canada, it may be difficult to identify patients who are affected with these rare conditions. This article discusses: 1) the utility of newborn screening and diagnosis of metabolic diseases in immigrant and refugee populations, with complex medical presentations, and 2) a recent diagnosis of succinic semialdehyde dehydrogenase deficiency (an IEM) in a refugee child past the age limit of NBS. An increasingly complicated and diverse refugee population requires a need for revision of existing healthcare practices pertaining to the diagnosis of rare diseases.

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Inborn Errors of Metabolism

Cited by 104 publications

References 39 publications

Amino Acids Profiling for the Diagnosis of Metabolic Disorders

Amino Acids Profiling for the Diagnosis of Metabolic Disorders

Metabolomics enables precision medicine: “A White Paper, Community Perspective”

Inborn errors of metabolism in newcomer and refugee populations in Ontario, CA

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