Late onset GM2 gangliosidosis: an alpha-locus genetic compound with near normal hexosaminidase activity.

A non-Jewish child with late onset GM2 gangliosidosis is described. Tissues from the patient had near normal hexosaminidase A (hex A) activity using 4-methylumbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranoside (MU-glcNAc) as substrate, and deficient activity when assayed with the 6-sulphate derivative of MU-glcNAc (MU-glcNAcS) or GM2 in the presence of activator. We present evidence that this patient is a genetic compound for different alpha-subunit mutations. The father's tissues have hex A activity in the heterozygote range when assayed with MU-glcNAcS, but normal activity using MU-glcNAc; the mother's tissues have activities toward both substrates in the heterozygote range. These results emphasize the pitfalls of using only MU-glcNAc for the diagnosis of unusual variants of GM2 gangliosidosis.