title: 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-alpha-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 alpha-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.
authors.affiliation: Molecular Genetic Analysis Group, Genzyme Corporation, Framingham, MA 01701, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Palmer
authors.forename: Hernan M
authors.initials: HM
authors.lastname: Amartino
authors.forename: Gabriela
authors.initials: G
authors.lastname: Niizawa
authors.forename: Mariana
authors.initials: M
authors.lastname: Blanco
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Pomponio
authors.forename: Nestor A
authors.initials: NA
authors.lastname: Chamoles
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001118:Argentina / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006009:Glycogen Storage Disease Type II / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000520:alpha-Glucosidases / Q000235:genetics* / Q000378:metabolism
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases