Alterations in specific activity of lysosomal alpha-glucosidase in cystic fibrosis.

Cultured skin fibroblasts derived from patients with cystic fibrosis contain 2.1-fold more acid alpha-glucosidase (EC 3.2.1.3) than normal fibroblasts. This difference is amplified to 2.3-fold when the cells are extracted in Triton X-100. In a study of 14 fibroblast cell lines derived from CF homozygotes and heterozygotes, normal individuals and patients with other recessively inherited disorders, normal individuals could be distinguished from either CF homozygotes or heterozygotes based on the ratio of acid alpha-glucosidase to beta-hexosaminidase when fibroblasts were extracted in either water or Triton X-100. However, the best distinction could be made with water extracts as there was no overlap among individual data points in the three categories. The acid to neural alpha-glucosidase ratio only distinguished CF homozygotes from normal individuals when cells were extracted in Triton X-100. The use of a ratio relationship of acid alpha-glucosidase with beta-hexosaminidase allows the comparison of data from multiple experiments on different days of assay and on cells at different passage numbers. These results suggest that alpha glucosidase may have a role in the primary defect in cystic fibrosis.