Abstrakt
Late-onset Tay-Sachs disease is a form of GM2 gangliosidosis with the first manifestation in adolescence to young adulthood. We present clinical and paraclinical findings in two sisters (19 and 29 years).
Speech impairment and clumsiness as the initial signs were followed by progressive proximal weakness in the lower extremities. Electromyography showed involvement of the lower motor neuron.
Molecular genetic testing brought no evidence of deletion within the SMN1 (survival of motor neuron) gene. Magnetic resonance imaging of the brain revealed marked cerebellar atrophy.
Marked decrease in beta-hexosaminidase A activity was found in the serum, plasma and leukocytes. DNA analysis of the HEXA gene identified heterozygous mutations: c.805G>A and c.1123delG.
It took 12 years to establish the diagnosis in the older sister. We recommend considering late-onset Tay-Sachs disease for the differential diagnosis of patients with clinical signs suggesting spinal muscular atrophy or spinocerebellar ataxia.
Accurate diagnosis may be of prospective significance in terms of therapeutic management.