Inborn Errors of Metabolism: Challenges and Management

Das, Subir Kumar

doi:10.1007/s12291-013-0371-7

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…Different classifications have emerged to categorize IEM diseases to enable easier clinical and laboratory diagnosis and facilitate treatment [53] such as pathophysiological classification of IEMs, (Figure 4). IEMs were assorted as disorders of carbohydrate metabolism, disorders of amino acid metabolism, disorders of organic acid metabolism, and lysosomal storage diseases [54]. However, more complex classification systems have recently been proposed [55].…”

Section: Classificationsmentioning

confidence: 99%

Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics

2019

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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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Section: Classificationsmentioning

confidence: 99%

Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics

2019

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“…Despite this, the potential for extending existing management strategies employed in high-income settings to lower resourced populations has much potential to impact on global IEM morbidity and mortality [ 50 ]. In LMICs where access to paediatric endocrinology expertise is often limited or non-existent, even with an accurate diagnosis of an IEM, appropriate management can be difficult to provide [ 50 , 51 ]. The development and propagation of clear national and international protocols for managing IEM and associated metabolic crises could provide one avenue of improving the standard of care for this important patient group.…”

Section: Discussionmentioning

confidence: 99%

Global birth prevalence and mortality from inborn errors of metabolism: a systematic analysis of the evidence

Waters¹,

Rudan²,

Woolham³

et al. 2018

Journal of Global Health

142

118

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BackgroundInborn errors of metabolism (IEM) are a group of over 500 heterogeneous disorders resulting from a defect in functioning of an intermediate metabolic pathway. Individually rare, their cumulative incidence is thought to be high, but it has not yet been estimated globally. Although outcomes can often be good if recognised early, IEM carry a high fatality rate if not diagnosed. As a result, IEM may contribute significantly to the burden of non-communicable childhood morbidity.MethodsWe conducted a systematic literature review of birth prevalence and case fatality of IEM globally, with search dates set from 1980 to 2017. Using random-effects meta-analysis, we estimated birth prevalence of separate classes of IEM and all-cause IEM, split by geographical region. We also estimated levels of parental consanguinity in IEM cases and global case fatality rates and resultant child deaths from all-cause IEM.Findings49 studies met our selection criteria. We estimate the global birth prevalence of all-cause IEM to be 50.9 per 100 000 live births (95% confidence intervals (CI) = 43.4-58.4). Regional pooled birth prevalence rates showed the highest rates of IEM to be in the Eastern Mediterranean region (75.7 per 100 000 live births, 95% CI = 50.0-101.4), correlating with a higher observed rate of parental consanguinity in studies from this area. We estimate case fatality rates to be 33% or higher in low- and middle-income countries (LMICs), resulting in a minimum of 23 529 deaths from IEM per year globally (95% CI = 20 382-27 427), accounting for 0.4% of all child deaths worldwide.ConclusionsIEM represent a significant cause of global child morbidity and mortality, comprising a notable proportion of child deaths currently not delineated in global modelling efforts. Our data highlight the need for policy focus on enhanced laboratory capacity for screening and diagnosis, community interventions to tackle parental consanguinity, and increased awareness and knowledge regarding management of IEM, particularly in LMICs.

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“…6,7 Classification of IEMs Traditionally, IEMs have been classified as disorders of metabolic pathways of carbohydrates, amino acids, lipids, organic acids, lysosomal storage, mitochondrial, peroxisomal, purine and pyrimidine disorders. 8 However, a recently updated classification of IEMs proposes three broad categories based on the size of metabolic compounds. These categories include small and simple molecules, large and complex molecules, and have implications in energy metabolism (Figure 1-A).…”

Section: Inborn Errors Of Metabolismmentioning

confidence: 99%

Closing the gap: an urgent need for newborn screening of organic acid disorders in developing countries

Vankwani,

Wasim,

Mirza

et al. 2024

J Pak Med Assoc

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Organic acid disorders are rare inherited metabolic disorders of key metabolic pathways. For the identification of specific organic acids, investigation of urinary metabolites and genetic testing are required through newborn screening programmes. Delayed diagnosis leads to complications, such as cardiac attacks, respiratory problems, neuro-developmental disorders, intellectual disability, and even premature death. The burden of such inherited disorders is quite high in developing countries of South Asia due to high rate of consanguinity in the region. Unfortunately, such disorders are left untreated due to the lack of screening facilities in such countries. The current narrative review was planned to highlight the urgent need for closing this gap and implementing effective newborn screening programmes for organic acid disorders in developing countries. ---Continue

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Inborn Errors of Metabolism: Challenges and Management

Cited by 7 publications

References 16 publications

Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics

Inborn Errors of Metabolism in the Era of Untargeted Metabolomics and Lipidomics

Global birth prevalence and mortality from inborn errors of metabolism: a systematic analysis of the evidence

Closing the gap: an urgent need for newborn screening of organic acid disorders in developing countries

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