title: c.1437G>A intron 9 substitution on acid α-glucosidase gene associated with classic infantile-onset Pompe disease phenotype.
abstract: Pompe disease, or glycogen storage disease type II (GSD2), an autosomal recessive disease first described by Joannes Cassianus Pompe (1901-1945), causes deficient activity of acid α-glucosidase (GAA) enzyme. GAA catalyses α 1,4 and α 1,6 glucosidic linkages in lysosomes; destruction of these linkages permits glycogen to be separated into glucose and later used for energy. Without proper function of this enzyme, glycogen accumulates in lysosome, causing muscle hypotonia. We report a previously undescribed association of c.1437G>A intron 9 substitution on the GAA gene with severe infantile-onset Pompe disease in a deceased proband and carrier status in four of five surviving family members. Previous authors have found late-onset or moderate severity infantile-onset Pompe disease associated with this allelic variation. Our proband's family's village was suspicious for locally endemic disease. While our proband developed all features of classic infantile onset GSD2, socioeconomic and geographic factors initially suggested an infectious aetiology.
authors.affiliation: Department of Applied Physiology, FSRG deGruyter-McKusick Institute of Health Sciences, Buckhannon, West Virginia, USA.
authors.forename: Andrés
authors.initials: A
authors.lastname: Morales
authors.affiliation: Department of Applied Physiology, FSRG deGruyter-McKusick Institute of Health Sciences, Buckhannon, West Virginia, USA.
authors.forename: Mikaela I
authors.identifier: http://orcid.org/0000-0003-3134-1580
authors.initials: MI
authors.lastname: Poling
authors.affiliation: Department of Applied Physiology, FSRG deGruyter-McKusick Institute of Health Sciences, Buckhannon, West Virginia, USA.
authors.forename: Marco T
authors.initials: MT
authors.lastname: Páez
authors.affiliation: Department of Applied Physiology, FSRG deGruyter-McKusick Institute of Health Sciences, Buckhannon, West Virginia, USA.
authors.forename: Julio
authors.initials: J
authors.lastname: Cabrera
authors.affiliation: Department of Applied Physiology, FSRG deGruyter-McKusick Institute of Health Sciences, Buckhannon, West Virginia, USA.
authors.forename: Rodger J
authors.initials: RJ
authors.lastname: McCormick
mesh_terms: D000483:Alleles; D005190:Family; D006580:Genetic Carrier Screening; D005838:Genotype; D006003:Glycogen / Q000378:metabolism*; D006009:Glycogen Storage Disease Type II / Q000235:genetics*; D006801:Humans; D007223:Infant; D007438:Introns; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D009123:Muscle Hypotonia / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D000520:alpha-Glucosidases / Q000235:genetics*
chemical_list: D006003:Glycogen; D000520:alpha-Glucosidases