Prenatal and postnatal studies of a late infantile GM2 gangliosidosis in a family of Syrian origin: a possible B1 variant

Abstract

We describe late infantile Tay-Sachs disease with high residual hexosaminidase A activity in two siblings of a Syrian Druze family. The patients' leukocytes had 26% of normal hexosaminidase A activity when tested with the conventional fluorogenic substrate 4-methyl-umbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranoside (4-MUG) and only about 10% when assayed with the sulfated substrate, 4-methyl-umbelliferal- beta-N-acetyl-glucosamine-6-sulfate (4-MUGS). According to the standard procedure of the heterozygote screening program (employing 4-MUG and heat inactivation), the parents were not diagnosed as an at-risk couple since the father was classified as a noncarrier. However, both parents' levels were clearly within the carrier range on the basis of 4-MUGS. The unique catalytic characteristics of the patients' enzyme forward the assumption that the affected sibs are B1 variants. The parents' enzymatic levels, together with their known consanguinity, might indicate that these patients are homozygotes for the rare mutation and not genetic compounds as has been documented for most of the infantile B1 variants. To the best of our knowledge this is the first reported case of B1 variant in a child of that extraction.