GM2 Gangliosidosis with a Motor Neuron Disease Phenotype: Clinical Heterogeneity of Hexosaminidase Deficiency Disease

The existence of families in which amyotrophic lateral sclerosis (ALS) is present, transmitted by an autosomal dominant trait, is well-known. In contrast with these more common cases, only a few familial cases occur with a pattern suggesting autosomal recessive inheritance. These genetic cases have recently stimulated research into the genetic dismetabolic conditions that could cause a phenotype similar to ALS or motor neuron diseases. In such families with atypical ALS cases, several typical Tay Sachs1 disease patients have been found[l]. In a screening program for Tay Sachs' disease, several cases with a motor neuron phenotype and an absence of hexosaminidase activity were found [2]. The same enzyme defect has been reported in young patients with a phenotype similar to juvenile muscular atrophy, Kugelberg-Welander phenotype [3], confirming that primary pathological changes of anterior horn cells can be possible in several cases with juvenile, infantile and adult forms of GM2 gangliosidosis. These forms are clinically characterized by a slow evolution and biochemically by an incomplete absence of hexosaminidase A or B or both.