Loss-of-function mutations in BCKDHA or BCKDHB cause MSUD

Stable Identifier
R-HSA-9865125
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Loss-of-function mutations in BCKDHA or BCKDHB cause MSUD
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Mutations in either of the protein subunits of the E1 decarboxylase subcomplex of BCKDH are associated with Maple Syrup Urine Disease 1 (MSUD1).
Mutations of residues in BCKDHA that participate in subunit associations or that form part of the hydrophobic core destabilize the overall assembly of BCKDH and are associated with classic Maple Syrup Urine Disease 1A (Aevarsson et al, 2000; reviewed in Straus et al, 2020; Biswas et al, 2019). Mutations of BCKDHA with less drastic effects on structural stability of the overall BCKDH complex are generally associated with intermediate or intermittent forms of MSUD, and are not annotated in this pathway (reviewed in Strauss et al, 2020)

Mutations in BCKDHB appear to be causative in 35% of MSUD cases(reviewed in Strauss et al, 2020). Classic Maple Syrup Disease 1B is associated with severe loss-of-function mutations in BCKDHB that destabilize the protein interaction interfaces and compromise structural integrity of the complex (reviewed in Straus et al, 2020; Biswas et al, 2019). Less detrimental mutations in BCKDHB are not annotated in this pathway and are generally associated with intermediate or intermittent forms of MSUD (reviewed in Strauss et al, 2020).
Literature References
PubMed ID Title Journal Year
20301495 Maple Syrup Urine Disease

Puffenberger, EG, Strauss, KA, Carson, VJ

2006
10745006 Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease.

Hol, WG, Turley, S, Chuang, DT, Chuang, JL, Wynn, RM, Aevarsson, A

Structure Fold Des 2000
31084571 Role of branched-chain amino acid-catabolizing enzymes in intertissue signaling, metabolic remodeling, and energy homeostasis

Biswas, D, Pulinilkunnil, T, Duffley, L

FASEB J 2019
Participants
Events
Participates
as an event of
Disease
Name Identifier Synonyms
maple syrup urine disease DOID:9269 dihydrolipoamide dehydrogenase deficiency
Authored
Rothfels, K  (2024-07-29)
Reviewed
D'Eustachio, P  (2024-08-18)
Created
Rothfels, K  (2024-03-08)
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