Motor neuron disease and adult hexosaminidase a deficiency in two families: Evidence for multisystem degeneration

Abstract

We studied three patients from two unrelated families with adult hexosaminidase A deficiency. A 30‐year‐old, non‐Jewish proband in the first family had juvenile amyotrophic lateral sclerosis that evolved to mild demetia, ataxia, and axonal (neuronal) motor‐sensory peripheral neuropathy. A 36‐year‐old Jewish proband in the second family had “pure” spinal muscular atrophy. One supposedly healthy brother of the first proband was found to have borderline IQ, mild spasicity, ataxia but no evidence of motor neuron disease. Marked cerebellar atrophy was detected by head scans in all three patients. In both probands electromyograms were chacteriszed prominent, complex repetitive discharges in many muscles. Hexosaminidase A activities against the artificial substrate were similar to those reported in infantile Tay‐Sachs disease; however, the hexosaminidase A level against GM₂ substrates was higher than that found infantile Tay‐Sachs disease. The hexosaminidase A levels of the parents were in the heterozygous range. Motor neuron disease in our patients and in those previously described appears to be park of a multisystem degeneration of the nervous system.