Late‐onset Tay−Sachs disease presenting with a neuromuscular phenotype—a case series

Abstract

AbstractBackground and purposeTay−Sachs disease is a rare and often fatal, autosomal recessive, lysosomal storage disease. Deficiency in β‐hexosaminidase leads to accumulation of GM2 ganglioside resulting in neuronal swelling and degeneration. Typical onset is in infancy with developmental regression and early death. Late‐onset Tay−Sachs disease (LOTS) is extremely rare, especially in the non‐Ashkenazi Jewish population, and is characterized by a more indolent presentation typically encompassing features of cerebellar and anterior horn cell dysfunction in addition to extrapyramidal and neuropsychiatric symptoms.CasesA case series of four unrelated patients of non‐Ashkenazi Jewish origin with a predominantly, and in some cases pure, neuromuscular phenotype with evidence of a motor neuronopathy on electromyography is presented. Cerebellar atrophy, reported to be a ubiquitous feature in LOTS, was absent in all patients.ConclusionThis case series provides evidence to support a pure neuromuscular phenotype in LOTS, which should be considered in the differential diagnosis of anterior horn cell disorders.