Reactome | Glycogen storage disease type II (GAA)

Glycogen storage disease type II (GAA)

Stable Identifier

R-HSA-5357609

Type

Pathway

Species

Homo sapiens

Synonyms

GSD II

ReviewStatus

5/5

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Glycogen storage disease type II (GSD II - Pompe's disease) is caused by mutations that reduce or eliminate the activity of lysosomal alpha-glucosidase (GAA) (Hers 1963). The presentation of GSD II varies with the severity of the mutation: patients with little or no GAA activity are affected shortly after birth and multiple tissues are severely affected. Patients with higher levels of GAA activity present later in life, often with symptoms restricted tocardiac and skeletal muscle (Leslie & Tinkle). At a cellular level, symptoms of the disease are due to accumulation of structurally normal glycogen in lysosomes. Glycogen, thought to enter lysosomes via autophagy, is fully degraded by GAA (Brown et al. 1970), but accumulates if the enzyme is absent or reduced in activity.

The two mutant alleles annotated here are associated with near-complete loss of enzyme activity and early onset of disease (Hermans et al. 1991; Zhong et al. 1991). Many other mutant alleles have been described and their residual activities correlated with disease presentation (e.g., Kroos et al. 2012).

Literature References

PubMed ID	Title	Journal	Year
	Glycogen Storage Disease Type II (Pompe Disease) Tinkle, BT, Leslie, N
13954110	alpha-Glucosidase deficiency in generalized glycogen-storage disease (Pompe's disease) Hers, HG	Biochem. J.	1963
1898413	Identification of a point mutation in the human lysosomal alpha-glucosidase gene causing infantile glycogenosis type II Kroos, MA, Reuser, AJ, Hermans, MM, Oostra, BA, de Graaff, E, Wisselaar, HA	Biochem. Biophys. Res. Commun.	1991
1652892	Identification of a missense mutation in one allele of a patient with Pompe disease, and use of endonuclease digestion of PCR-amplified RNA to demonstrate lack of mRNA expression from the second allele Tzall, S, Zhong, N, Hirschhorn, R, Martiniuk, F	Am. J. Hum. Genet.	1991
22644586	Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants Kroos, MA, Reuser, AJ, Pomponio, RJ, Halley, DJ, Michelakakis, H, Van der Ploeg, AT, Hoogeveen-Westerveld, M	Hum. Mutat.	2012
5264799	Simultaneous absence of alpha-1,4-glucosidase and alpha-1,6-glucosidase activities (pH 4) in tissues of children with type II glycogen storage disease Brown, BI, Jeffrey, PL, Brown, DH	Biochemistry	1970

Participants

Events

Defective GAA does not hydrolyze lysosomal glycogen (Homo sapiens)

Participates

as an event of

Glycogen storage diseases (Homo sapiens)

Disease

Name	Identifier	Synonyms
glycogen storage disease II	DOID:2752	Lysosomal alpha-1,4-glucosidase deficiency (disorder), deficiency of glucoamylase, glycogen storage disease type II, acid maltase deficiency, deficiency of maltase, Glycogen storage disease, type II (disorder), Pompe's disease, Generalized glycogenosis (disorder), Glycogenosis, type 2

Authored

D'Eustachio, P (2014-03-25)

Reviewed

Jassal, B (2015-08-17)

Created

D'Eustachio, P (2014-03-25)