N-acetyl-beta-hexosaminidase B deficiency in cultured fibroblasts from a patient with progressive motor neuron disease.

A patient with a 20-year history of progressive motor neuron disease was previously found to have profoundly low levels of N-acetyl-beta-hexosaminidase (Hex) in serum and leukocytes; Hex activity in cultured skin fibroblasts was in the low normal range. By thermal inactivation and cellulose acetate electrophoresis, the residual activity appeared to be Hex A. In the present study, the residual activity in cultured skin fibroblasts was further characterized as Hex A by thermal inactivation at reduced temperatures and ion exchange chromatography; no evidence was obtained for a diffusible inhibitor of Hex activity. After labeling with [3H]leucine, immunoprecipitation with polyclonal antibody to Hex B, and SDS-polyacrylamide gel electrophoresis, both alpha and beta polypeptide chains were visualized, confirming the presence of Hex A. The results suggest that, in the patient's fibroblasts, a defect in beta-chain synthesis or processing precludes the self-association of beta-chains to form Hex B, but does not prevent the association of alpha- and beta-chains to form Hex A.