title: Km mutant of acid alpha-glucosidase in a case of cardiomyopathy without signs of skeletal muscle involvement.
abstract: A male patient is reported with a mutation of acid alpha-glucosidase causing an altered Km toward natural substrates. Cardiac arrhythmia was found at 12 years of age, and he died of heart failure at 15 years. No skeletal muscle involvement was observed either clinically or histologically. Acid alpha-glucosidase activity in fibroblasts was moderately low (43% of the control mean) with normal Km for 4-methylumbelliferyl alpha-D-glucoside. The hydrolysis of glycogen was markedly decreased (14% of the control mean), and the Km for maltose was increased 4-fold and for glycogen 5-fold. The biosynthesis and the posttranslational processing of the mutant enzyme appeared normal, but the total amount of the enzyme was lower than normal. This mutant enzyme comigrated with normal acid alpha-glucosidase on starch gel electrophoresis, and not with the rare isozyme, acid alpha-glucosidase 2. A possible role of this mutant enzyme in the pathogenesis of this disease and the relationship to glycogenesis II are discussed.
authors.affiliation: Division of Inherited Metabolic Disease, National Institute of Neuroscience, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
authors.forename: K
authors.initials: K
authors.lastname: Omura
authors.forename: G
authors.initials: G
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Awa
authors.forename: M
authors.initials: M
authors.lastname: Kroos
authors.forename: A J
authors.initials: AJ
authors.lastname: Reuser
mesh_terms: D000293:Adolescent; D001145:Arrhythmias, Cardiac / Q000209:etiology; D009202:Cardiomyopathies / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005347:Fibroblasts / Q000201:enzymology; D006003:Glycogen / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D007700:Kinetics; D008297:Male; D009132:Muscles / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D013379:Substrate Specificity; D000520:alpha-Glucosidases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D006003:Glycogen; D000520:alpha-Glucosidases