Tay-Sachs disease is a genetically determined neurodegenerative disorder, 
resulting from mutations of the hexosaminidase (Hex) A gene coding for the 
alpha-subunit of beta-D-N-acetyl-hexosaminidase. Clinically, there is severe 
encephalomyelopathy leading to death within the first few years of life. Hex A 
activity is usually absent in tissue and body fluids of these patients. Juvenile 
and adult Hex A deficiencies are less severe but rare variants with some 
residual Hex A activity. All these variants are most prevalent among Ashkenazi 
Jews. We describe a non-Jewish family in which four adult brothers and sisters 
had markedly reduced Hex A activities and onset of symptoms in the second decade 
of life. The phenotypical expression was remarkably homogeneous, consisting in a 
combination of slowly progressive motor neuron disease, ataxia and ocular motor 
disturbances. None of the patients were demented at this stage of their illness. 
Magnetic resonance studies showed severe cerebellar atrophy, but were otherwise 
normal. Hex A deficiency was established by biochemical measurements in the 
serum and skin fibroblasts using the fluorogenic substrates 4-MUG and 4-MUGS as 
well as by gel electrophoresis. Molecular genetic studies revealed that the 
patients are compound heterozygotes for the 'adult' mutation Gly269 --> Ser and 
the 'infantile' 4-base insertion in exon 11 of the Hex A gene.