Premium
Km mutant of acid α‐glucosidase in a case of cardiomyopathy without signs of skeletal muscle involvement
Author(s) -
Suzuki Yoshiyuki,
Tsuji Akihiko,
Omura Kiyoshi,
Nakamura Gen,
Awa Shoichi,
Kroos Marian,
Reuser Arnold J. J.
Publication year - 1988
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1988.tb03465.x
Subject(s) - glycogen storage disease , mutant , glycogen , glycogen debranching enzyme , enzyme , maltose , glycogen branching enzyme , isozyme , biochemistry , skeletal muscle , medicine , biology , glycogen storage disease type ii , endocrinology , cardiomyopathy , chemistry , glycogen synthase , enzyme replacement therapy , gene , heart failure , disease
A male patient is reported with a mutation of acid α‐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 α‐glucosidase activity in fibroblasts was moderately low (43% of the control mean) with normal Km for 4‐methylumbelliferyl α‐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 α‐glucosidase on starch gel electrophoresis, and not with the rare isozyme, acid α‐glucosidase 2. A possible role of this mutant enzyme in the pathogenesis of this disease and the relationship to glycogenosis II are discussed.