GM2 Gangliosidosis is an inherited dysmetabolic disease, characterized by accumulation of GM2 and GAz gangliosides in neuronal as well as in non-neuronal tissues. Biochemically the disorder can be due either to a deficiency of hexosaminidase isoenzyme A (Tay-Sachs form) or isoenzymes A and B (Sandhoff variant) or to absence of the activator protein of the enzyme (Sandhoff and Christomanov, 1979). Infantile, juvenile and adult phenotypes are known. Recently patients with lateonset disease with amyotrophic lateral sclerosis-like or Kugebelg-Welander phenotypes or spinocerebellar ataxia have been described, and a large heterogeneity is increasingly being discovered (Johnson, 1981; Federico, in press). In this report we describe two brothers, now 49 and 44 years old, presenting a slowly progressive ataxia, fasciculations, peripheral neuropathy and autonomic nervous system involvement, and biochemically, severe deficiency of both hexosaminidase (Hex) A and B isoenzymes. A preliminary report on these patients has been previously communicated (Guazzi et al., 1983).