Gene Summary
RefSeq / NCBIThis gene encodes lysosomal alpha-glucosidase, which is essential for the degradation of glycogen to glucose in lysosomes. The encoded preproprotein is proteolytically processed to generate multiple intermediate forms and the mature form of the enzyme. Defects in this gene are the cause of glycogen storage disease II, also known as Pompe's disease, which is an autosomal recessive disorder with a broad clinical spectrum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
Clinical Phenotype
Pompe disease (glycogen storage disease type II): ranges from classic infantile (cardiomegaly, hypotonia, death by 2 years untreated) to late-onset (slowly progressive proximal myopathy ± respiratory failure, no cardiac involvement).
Molecular Mechanism
Deficiency of lysosomal acid alpha-glucosidase leads to intra-lysosomal glycogen accumulation in muscle and other tissues. Vacuolar myopathy with PAS-positive vacuoles. Late-onset often caused by the common c.-32-13T>G splice variant, retaining some residual enzyme activity.
Clinical Hallmarks & Key Evidence
The 'cross sign' on muscle MRI — selective involvement of paraspinal and posterior thigh muscles — is characteristic of late-onset Pompe disease.
Carlier RY et al. J Inherit Metab Dis. 2011;34(4):923-30.
Acid alpha-glucosidase (GAA) enzyme activity can be measured on dried blood spot — used for newborn screening and diagnosis.
Kemper AR et al. Genet Med. 2017;19(12):1238-1244.
Enzyme replacement therapy (alglucosidase alfa, 2006; avalglucosidase alfa, 2021) is the standard of care; glycogen-reducing substrate therapy (miglustat) is investigational.
Van den Hout HM et al. Pediatrics. 2000;105(1):E17.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.