Late-onset hexosaminidase A deficiency mimicking primary lateral sclerosis.

The GM2 gangliosidosis are a group of metabolic disorders in which deficiency of a lysosomal enzyme, hexosaminidase A (Hex A), leads to an abnormal intracellular accumulation of lipids in neurons and glia. Total deficiency is responsible for a fatal infantile disorder, Tay-Sachs disease, characterized by involution in motor abilities, hypotonia, seizures and cortical blindness, with death around 5 or 6 years-old. Partial deficiency of enzyme activity is associated with a variety of late-onset (teenagers and young adults) neurological phenotypes, characterized by upper and lower motor neuron signs, cerebellar disturbances, parkinsonism, and psychosis or dementia in different combinations. Macular cherry red spots, which are typical for Tay-Sachs, are not apparent in these patients. All of the GM2 gangliosidosis subtypes are inherited in an autosomal recessive fashion and the differences in age at onset and disease course may be partly attributed to the underlying Hex A gene defect. Patients with infantile onset tend to be homozygous or compound heterozygote for severe, deleterious (“null”) alleles, whereas patients with late-onset disease have a combination of one severe and another allele associated with residual Hex A activity. Late onset GM2 gangliosidosis (LOGM2) is commonly included in the differential diagnosis of amyotrophic lateral sclerosis (ALS), due to the involvement of anterior horn cell, causing weakness, atrophy, cramps and fasciculations. We report a patient with unusual clinical features of isolated upper motor neuron (UMN) involvement, resembling primary lateral sclerosis (PLS).