[Late infantile and juvenile form of GM2-gangliosidosis variant B1].

Variant B1 is a rare form of GM2-gangliosidosis characterized by the presence of a mutation in the hexosaminidase A gene (HEXA) leading to a defect in the catalytic region of the alpha-subunit of beta-hexosaminidase A (alpha beta heterodymer). The mutated Hex A has almost normal activity against the natural synthetic substrates (4-methylumbelliferyl-N-acetyl-beta-D-glucosamine, 4MU-NAG) but is unable to hydrolyse GM2-ganglioside and the sulphated synthetic substrates (4MU-NAGS). The first and more frequent mutation described in the alpha-subunit gene associated to B1 variant GM2-gangliosidosis was a G533-->A transition (DN allele) resulting in Arg178His substitution.,Here, we report the clinical, enzymatic and molecular characterization in two variant B1 late infantile and juvenile cases. Both cases presented regression of mental skills leading to dementia, epilepsy and severe motor impairment with dystonic involuntary movements and quadriplegia. In the late infantile case (death at 5 years and 8 months), cherry-red spot was also present. Enzymatic assays were performed in fibroblasts, leukocytes and serum and confirmed the abnormally low beta-hexosaminidase A activity against sulphated substrate despite a normal or nearly normal total hexosaminidase activity (unsulphated substrates). The patient with the late infantile phenotype was found to be compound heterozygote for the DN allele whilst the juvenile form was homozygote for that mutation.,Variant B1 form of GM2-gangliosidosis is a rare and heterogeneous condition that must be kept in mind when evaluating neurodegenerative disorders associated with speech or gait disturbances, dystonia, seizures and pyramidal features.