Hexosaminidase A deficient adults: presence of alpha chain precursor in cultured skin fibroblasts

Abstract

Cultured skin fibroblasts from hexosaminidase A deficient adults synthesize the alpha and beta chain precursors of beta-hexosaminidase (EC 3.2.1.30) of the same molecular weight as that synthesized by normal fibroblasts. However, the amount of the alpha chain precursor is greatly reduced. The alpha chain precursor in secretions from these fibroblasts consists of 19% of the total beta-hexosaminidase secreted compared to about 50% in normal cells. Attempts to increase the amount of detectable cellular alpha chain precursor by addition of protease inhibitors or extensive extraction methods have failed. Mature alpha chains were not detected. The presence of alpha chain precursor in fibroblasts from hexosaminidase A deficient adults can be used to distinguish between them and true Tay-Sachs disease homozygotes.