Glycogenosis type II: protein and DNA analysis in five South African families from various ethnic origins.

The molecular nature of lysosomal alpha-glucosidase deficiency was studied in five South African families with glycogenosis type II. Distinct ethnic origins were represented. Two new mutant acid alpha-glucosidase alleles were discovered. In two infantile patients from a consanguineous Indian family we found for the first time an acid alpha-glucosidase precursor of reduced size. The mutant precursor appeared normally glycosylated and phosphorylated but was not processed to mature enzyme. Abnormalities of the mRNA were not obvious, but digestion of genomic DNA with HindIII, BglII, and StuI revealed for each enzyme a fragment of increased length. Heterozygosity was demonstrated in the parents. Complete lack of acid alpha-glucosidase mRNA, as well as deficiency of precursor synthesis, was observed in two black baby girls from unrelated families. In these cases the length of all restriction-enzyme fragments was normal. Reduced enzyme synthesis but normal processing was registered in juvenile and young adult Cape colored patients. The extensive heterogeneity of glycogenosis type II is emphasized in these studies on various ethnic groups. The newly discovered mutants are valuable for the understanding of clinical diversity as a result of allelic variation.