GAA across dismech

GAA (alpha glucosidase) is named by 3 disorder entries, all forms of Pompe disease (glycogen storage disease type II).

Normal function

ai-gene-review gives GAA's core molecular function as alpha-1,4-glucosidase activity, acting in glycogen catabolic process in the lysosomal lumen; and lysosome. This is the acid, lysosomal route of glycogen breakdown, separate from cytosolic glycogenolysis.

Causative records

All three entries type GAA as causative: Infantile-Onset Pompe Disease; Late-Onset Pompe Disease; and Pompe Disease, and all three record the variants as germline (Infantile-Onset Pompe Disease; Late-Onset Pompe Disease; and Pompe Disease).

The three entries place the gene on different molecular nodes, which is how they separate the clinical forms. The parent entry puts GAA on Lysosomal glycogen accumulation. The infantile-onset entry puts it on Near-complete acid alpha-glucosidase deficiency and on Absence of immunologically detectable GAA protein (CRIM-negative status), the null-allele state that predicts an antibody response to enzyme replacement. The late-onset entry puts it on Leaky GAA Splicing and Partial Residual Enzyme Activity, and records the functional impact there as partial loss of function. Nodes naming GAA conform to the module lysosomal_substrate_accumulation.

ClinGen rates GAA definitive for glycogen storage disease II, which is the Pompe Disease entry's own disease term. The infantile- and late-onset entries map to that disease only as a broader term, so the assertion is not recorded on them.

Where the layers agree

The KB's GAA nodes and the ai-gene-review core function share glycogen catabolic process as a GO process. ClinGen classifies GAA for 1 disease, and no dismech entry matched to it leaves the gene untyped (0).