Diseases of branched-chain amino acid catabolism

Stable Identifier
R-HSA-9865118
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Diseases of branched-chain amino acid catabolism
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Mutations in the genes that encode enzymes responsible for the catabolism of the branched-chain amino acids leucine, isoleucine and valine give rise to a number of inborn errors of metabolism (IEMs). Although IEMs are individually rare, collectively they are relatively common with an estimated overall prevalence of ~1:800 live births (Mak et al, 2013). The frequency of particular IEMs is also highly variable across different populations, a result in part of founder effects in closed populations. For instance, although the overall frequency of Maple Syrup Urine disease is 1:185,000 live births (Strauss et al, 2020), the frequency rises to 1:380 in some Old Order Mennonite communities (Fisher et al, 1991).
Accumulation of toxic intermediary metabolites causes a range of clinical phenotypes in patients with IEMs including metabolic acidosis, vomiting, seizures, psychomotor and developmental delays and death (reviewed in Schrier Vergano et al, 2022; Holoček, 2018; Neinast et al, 2019).
Literature References
PubMed ID Title Journal Year
35773536 Inborn Errors of Metabolism: Becoming Ready for Rare

Vergano, SAS

Pediatr Rev 2022
20301495 Maple Syrup Urine Disease

Puffenberger, EG, Strauss, KA, Carson, VJ

2006
24295058 Inborn errors of metabolism and expanded newborn screening: review and update

Mak, CM, Chan, AY, Lam, CW, Lee, HC

Crit Rev Clin Lab Sci 2013
1885764 Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation in E1 alpha impedes assembly of the E1 component of branched-chain alpha-keto acid dehydrogenase complex

Fisher, CR, Fisher, CW, Chuang, JL, Chuang, DT, Star, RA, Cox, RP

J Clin Invest 1991
30485760 Branched Chain Amino Acids

Arany, Z, Murashige, D, Neinast, M

Annu. Rev. Physiol. 2019
29755574 Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements

Holeček, M

Nutr Metab (Lond) 2018
Participants
Events
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Disease
Name Identifier Synonyms
amino acid metabolic disorder DOID:9252 inborn errors of amino acid metabolism
Authored
Rothfels, K  (2024-07-29)
Reviewed
D'Eustachio, P  (2024-08-18)
Created
Rothfels, K  (2024-03-08)
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