Pompe disease (glycogen storage disease type II) in Argentineans: Clinical manifestations and identification of 9 novel mutations

Abstract Pompe disease is an autosomal recessive disorder caused by a deficiency in 1,4-α-glucosidase (EC.3.2.1.3), the enzyme required to hydrolyze lysosomal glycogen to glucose. While previous studies have focused on Pompe patients from Europe, the United States, and Taiwan, we have analyzed a group of South American Pompe patients to better understand the molecular basis of their disease. From 14 Argentinean patients diagnosed with either infantile or late-onset disease, we identified 14 distinct mutations in the acid α-glucosidase (GAA) gene including nine novel variants (c.236_246del, c.377G > A, c.1099T > C, c.1397T > G, c.1755-1G > A, c.1802C > G, c.1978C > T, c.2281delGinsAT, and c.2608C > T). Three different families displayed the c.377G > A allelic variant, suggesting a higher frequency among a subset of Argentineans. Comparison of patients with similar or identical variations in the GAA gene highlights the phenotypic diversity of late-onset disease and supports a role for other genetic and environmental factors in disease presentation.