a-Locus Hexosaminidase Genetic Compound with Juvenile Gangliosidosis Phenotype: Clinical, Genetic, and Biochemical Studies

A 3-year-old boy developed progressive neurological deterioration in his third year, characterized by dementia, ataxia, myoclonic jerks, and bilateral macular cherry-red spots. Hexosaminidase A (HEX A) was partially decreased in the patient's serum, leukocytes, and cultured skin fibroblasts. Hexosaminidase was studied in serum and leukocytes from family members. Four members of the paternal branch appeared to be carriers of classical infantile Tay-Sachs allele, HEXa2, probably receiving the gene from one great-grandparent of Ashkenazi origin. In the maternal branch, no one was a carrier of classical infantile Tay-Sachs disease, but five individuals were carriers of a milder a-locus defect. The patient, therefore, was a genetic compound of two different a-locus hexosaminidase mutations. At least 21 families with late-infantile or juvenile GM2 gangliosidosis have been reported, 18 of them with a-locus mutations, and three with /3-locus mutations. Genetic compounds of hexosaminidase have been reported in at least seven families, five with a-locus mutations and two with ,8-locus mutations. The compound had the phenotype of infantile Tay-Sachs disease in one family, infantile Sandhoff disease in another, and the normal phenotype in the rest.