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Tay Sachs disease is a lethal neurodegenerative lysosomal storage disease. Patients typically present in childhood, but can present in adolescence and, rarely, adulthood. The disease is caused by deficient B-hexosaminidase A activity. We present a case of an adult male with late onset Tay Sachs disease, presenting as an adult onset motor neuronopathy.

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A 42 year old right-handed man presented with progressive lower limb proximal weakness which began in his early thirties. Prior to this he was an active man, with normal milestones.  Examination was significant for wasting of the thighs with scanty fasciculations and Gower’s manoeuvre. There was mild weakness distally in the upper limbs, with proximal lower limb weakness. Reflexes were absent at the ankles bilaterally.

CK was elevated 1374 (<190). Initial clinical impression was of a possible limb girdle muscular dystrophy (LGMD); however, whole exome sequencing (WES) with analysis of LGMD genes was negative. Subsequent nerve conduction studies were normal, but electromyography (EMG) showed complex repetitive discharges, fasciculation potentials, fibrillations and profuse and large amplitude positive sharp waves, favouring denervation as opposed to myopathy. SMN1 testing was normal and reanalysis of the WES data in light of the new clinical information revealed a homozygous pathogenic variant in HEXA c.805G>A (p.Gly269Ser).

This case highlights the importance of the neurophysiological phenotype in patients with neuromuscular disease. Tay Sachs disease should be considered in the differential for adult onset non length dependent motor neuronopathy, albeit a rare cause.