Pompe Disease, also known as Glycogen Storage Disease Type II or acid maltase deficiency, is an autosomal recessive lysosomal storage disorder caused by mutations in the GAA gene that lead to absence or deficiency of the enzyme acid alpha-glucosidase. Glycogen breakdown in the lysosomes is impaired and its accumulation causes progressive damage in multiple tissues, especially cardiac and skeletal muscle. Pompe Disease occurs in all races has an overall estimated incidence of 1 in 40,000 births.¹

Pompe Disease is broadly classified into infantile-onset (with classic and non-classic types) and late-onset (with childhood, juvenile, and adult-onset types). Classic infantile-onset disease may be seen in utero or within the first month of life, with symptoms including low muscle tone, weakness, poor feeding, cardiomyopathy, and respiratory distress. If untreated, cardiopulmonary insufficiency often leads to death in the first year. Late-onset disease presents from the first to the sixth decade of life with slowly progressive skeletal muscle weakness and without significant cardiac involvement. In these cases, respiratory muscle weakness is the leading cause of death. Age of onset and severity roughly correspond to residual enzyme level which is determined, in part, by the identity and combination of mutations present in the affected individual. Prompt diagnosis allows early referral for enzyme replacement therapy which can improve or stabilize symptoms and quality of life, especially in the infantile onset group.¹

Genetic testing is a valuable complement to biochemical diagnostic testing. Knowledge of familial mutations facilitates carrier testing for relatives, which cannot be done reliably with biochemical testing. Also, some genotypephenotype correlation has been observed for the more common mutations which may help classify disease type.