title: A case of childhood Pompe disease demonstrating phenotypic variability of p.Asp645Asn.
abstract: A six-year-old child presented at 8 months of age with proximal muscle weakness and mild cardiac hypertrophy. Some alpha-glucosidase activity was detected in muscle but not in fibroblasts. As none of the two pathogenic mutations, [c.1933G>A]+[c.2702T>A] (Asp645Asn/Leu901Gln), led to detectable alpha-glucosidase activity upon expression in COS cells, the phenotype of the patient remained unexplained. A functionally comparable set of mutations, Asp645Asn/insGnt2243, was reported previously to cause classic infantile Pompe disease [Biochem Biophys Res Commun 244 (1998) 921]. We conclude that secondary genetic or environmental factors can be decisive for the phenotypic outcome of classic infantile versus childhood Pompe disease, when the acid alpha-glucosidase activity is extremely low.
authors.affiliation: Department of Clinical Genetics, Erasmus MC, P.O. Box 1738, Rotterdam 3000 DR, The Netherlands.
authors.forename: Marian A
authors.initials: MA
authors.lastname: Kroos
authors.forename: Janbernd
authors.initials: J
authors.lastname: Kirschner
authors.forename: Frank N
authors.initials: FN
authors.lastname: Gellerich
authors.forename: Monique M P
authors.initials: MM
authors.lastname: Hermans
authors.forename: Ans T
authors.initials: AT
authors.lastname: Van Der Ploeg
authors.forename: Arnold J J
authors.initials: AJ
authors.lastname: Reuser
authors.forename: Rudolf
authors.initials: R
authors.lastname: Korinthenberg
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D015153:Blotting, Western / Q000379:methods; D019556:COS Cells; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D019560:Echocardiography, Three-Dimensional / Q000379:methods; D005347:Fibroblasts / Q000378:metabolism; D006009:Glycogen Storage Disease Type II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D014162:Transfection / Q000379:methods; D000520:alpha-Glucosidases / Q000235:genetics* / Q000378:metabolism
chemical_list: D001224:Aspartic Acid; D001216:Asparagine; D000520:alpha-Glucosidases