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Lysosomal acid alpha-glucosidase deficiency (Pompe disease, glycogen storage disease II, acid maltase deficiency)

J Lawrence Merritt II, MD
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS


Acid alpha-glucosidase (GAA, also called acid maltase) deficiency (Pompe disease, MIM #232300) was the first identified lysosomal storage disease. It is also classified as glycogen storage disease type II (GSD II) (table 1) [1]. GAA deficiency leads to accumulation of glycogen within the lysosome in all tissues (figure 1). The defect in the lysosomal GAA enzyme affects lysosomal-mediated degradation of glycogenesis, unlike the defects in most other GSDs that affect glycogen synthesis or regulation of energy production. Therapies developed for GAA deficiency resemble those used for other lysosomal storage diseases since they share similar disease mechanisms. (See "Inborn errors of metabolism: Classification", section on 'Lysosomal storage disorders'.)

This topic reviews Pompe disease due to GAA deficiency. An overview of GSDs due to defects in glycogen synthesis and energy production is presented separately. (See "Overview of inherited disorders of glucose and glycogen metabolism".)


The estimated incidence of GAA deficiency was 1 in 40,000 in a study in the Netherlands that screened newborn blood spots for the three common mutant alleles in that population [2]. The predicted incidence based upon carrier frequencies was 1 in 138,000 for classic infantile disease and 1 in 57,000 for late-onset disease. A study investigating strategies for newborn screening in an Austrian population found a higher incidence (1 in 8686) for the early- and late-onset forms combined [3].


Lysosomal GAA is needed to hydrolyze both alpha-1,4- and alpha-1,6-glucosidic linkages in the low pH environment of the lysosome. Deficiency of the enzyme leads to accumulation of glycogen in lysosomes and in the cytoplasm, resulting in tissue destruction [4]. The effect of the enzyme deficiency may extend to vesicle systems that are linked to lysosomes and may also affect receptors, such as glucose transporter 4, that cycle through these organelles [5]. Enzyme activity correlates with genotype and is absent or minimal in patients with infantile-onset phenotype and variably reduced in those with late-onset phenotype [6].


Lysosomal GAA deficiency is an autosomal recessive disorder with considerable allelic heterogeneity. It is caused by mutations in the gene encoding lysosomal acid alpha-1,4-glucosidase (GAA), located at 17q25.2-q25.3 [7,8]. More than 500 mutations causing the disorder have been reported [9]. Common mutations have been described in a number of ethnic populations, including a pseudodeficiency mutation (a mutation that reduces GAA enzyme activity, but does not cause disease) [10].


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Literature review current through: Sep 2016. | This topic last updated: Apr 6, 2016.
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