Genetic heterogeneity in acid α-glucosidase deficiency

N. G. Beratis, G. U. LaBadie, K. Hirschhorn

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46 Scopus citations


Several clinical forms of acid α-glucosidase deficiency have been described. Our study was planned to identify differences at the molecular level in acid α-glucosidase deficiency. Of 9 fibroblast strains derived from patients with the infantile form of the disease, 8 were crossreacting material (CRM)-negative and one CRM-positive. This was demonstrated by both agar immunodiffusion and immunotitration. No difference in apparent enzymatic activity was observed between CRM-negative and CRM-positive infantile acid α-glucosidase deficiency fibroblasts. In 2 fibroblast strains with the adult form of acid α-glucosidase deficiency, rocket immunoelectrophoresis demonstrated a reduction in the amount of enzyme protein, which was directly proportional to the reduction in enzyme activity. In another fibroblast strain obtained from a patient with the adult form of the disease, the activity was within the range of the infantile form and no CRM could be identified. Fibroblasts with phenotype 2 of acid α-glucosidase, considered a normal variant, showed a reduction both in the amount of enzyme protein and in the ability of the enzyme to cleave glycogen. However, the catalytic activity for maltose was normal. The findings demonstrate extensive genetic heterogeneity in acid α-glucosidase deficiency. Molecular differences were identified both between the clinical forms of the disease and within the infantile and the adult forms of acid α-glucosidase deficiency. It remains unknown whether or not the enzyme deficiency in homozygotes for isozyme 2 of acid α-glucosidase will be sufficient to cause glycogen accumulation and lead to the development of muscular dystrophy-like disease later in life.

Original languageEnglish
Pages (from-to)21-33
Number of pages13
JournalAmerican Journal of Human Genetics
Issue number1
StatePublished - 1983
Externally publishedYes


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