Atypical presentation of late-onset Tay-Sachs disease.

INTRODUCTION

Late-onset Tay-Sachs disease (LOTS) is a lysosomal storage disease caused by deficient Beta-hexosaminidase A activity.

METHODS

We describe a 53-year-old woman who presented with adult-onset leg weakness, and whose initial diagnosis was progressive muscular atrophy without identifiable etiology. Development of cerebellar ataxia in mid-life prompted reassessment.

RESULTS

Beta-hexosaminidase A quantification assay demonstrated absence of the isozyme. Genetic testing identified compound heterozygous mutations in the HEXA gene, confirming the diagnosis of LOTS.

CONCLUSIONS

The phenotypic spectrum of LOTS includes motor neuronopathy, ataxia, choreoathetosis, neuropathy, and psychiatric symptoms in various combinations. This patient highlights the emergence of different clinical features over many years and emphasizes the need to consider LOTS in the differential diagnosis of progressive muscular atrophy.