Variant of GM2-gangliosidosis with hexosaminidase A having a severely changed substrate specificity.

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Abstract
The levels of hexosaminidase A activity in cultivated fibroblasts of two patients with GM2‐gangliosidosis were close to the normal range with 4‐methylumbelliferyl‐beta‐D‐2‐acetamido‐2‐deoxyglucopyranoside and 4‐methylumbelliferyl‐beta‐D‐2‐acetamido‐2‐deoxygalactopyranoside as substrates, and the enzymes were normal in most parameters analyzed. However, the enzymes of both patients were almost completely inactive against two specific substrates for hexosaminidase A, rho‐nitrophenyl‐6‐sulfo‐2‐acetamido‐2‐deoxy‐beta‐D‐glucopyranoside, and ganglioside GM2 in the presence of GM2‐activator. Fibroblast extracts of both patients showed normal hexosaminidase B and GM2‐activator activity, the latter was strongly decreased in two cases with variant AB. It is suggested that human hexosaminidase A may contain two different active sites which might be inactivated separately by different mutations.