Defective GBE1 does not catalyze branch formation in growing glycogen chains (liver)

Stable Identifier
Reaction [transition]
Homo sapiens
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Normally, cytosolic glycogen branching enzyme (GBE1) associated with glycogen granules transfers terminal alpha(1,4) glucose blocks to form alpha(1,6) branches on growing glycogen molecules of both liver and muscle types. In the absence of GBE1 activity, abnormal amylopectin-like glycogen with longer alpha(1,4) chains and fewer branch points forms in all tissues where glycogen is normally found. Presentation of the disease is clinically heterogeneous. The two missense mutant alleles annotated here, associated with near-complete loss of GBE1 activity, lead to progressive liver disease.A nonsense mutant allele R524X and a large internal deletion are also associated with this presentation, while a L224P missense mutation is associated with partial reduction of enzyme activity and nonprogressive liver disease (Bao et al. 1996) and other missense and nonsense mutations (e.g., H243R, R637X) are associated with absent enzyme activity and a neuromuscular disease presentation (Bruno et al. 2004). GBE1 deficiency is thus well-established as the molecular basis of GSD IV, but the basis of its variable presentation in children with little or no enzyme activity remains unclear.
Literature References
PubMed ID Title Journal Year
15452297 Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV)

Mosca, F, van Diggelen, OP, Pasquini, E, Morandi, L, Vilarinho, L, Assereto, S, Traverso, M, Tonoli, E, van Noort, G, Introvini, P, Alegria, A, Zara, F, Bruno, C, Minetti, C, Bado, M, Donati, MA, Gimpelev, M, Giuffrè, B, Mascelli, S, DiMauro, S, Mora, M, Cassandrini, D

Neurology 2004
8613547 Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene.

Wu, JY, Chen, Y-T, Kishnani, P, Bao, Y

J Clin Invest 1996
Catalyst Activity

1,4-alpha-glucan branching enzyme activity of GBE1 mutants [cytosol]

Normal reaction
Functional status

Loss of function of GBE1 mutants [cytosol]

Name Identifier Synonyms
glycogen storage disease IV DOID:2750 deficiency of 1,4-alpha-glucan branching enzyme, brancher deficiency glycogenosis, Branching-transferase deficiency glycogenosis (disorder), Amylopectinosis, Glycogen storage disease, type IV (disorder)
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