Objective: To describe a population of eight patients with Late Onset Tay Sachs (LOTS) disease and offer tips to aid in diagnosing this rare condition. Early diagnosis will be critical when disease modifying therapies are developed.

Background: LOTS is a rare autosomal recessive, lysosomal storage disorder due to hexosaminidase A deficiency. LOTS is frequently misdiagnosed leading to a significant delay in diagnosis.

Methods: We performed a retrospective chart review of eight LOTS patients referred to a large urban lysosomal storage disorders clinic. Demographic data, family history, clinical features (including age of onset, age at diagnosis, first symptoms, past medical and surgical history), genetic and metabolic tests, brain imaging and physical examination were analyzed.

Results: Mean age at diagnosis was 33.25 years (range 22-54 yrs) with symptom onset ranging from childhood to early adulthood. 50% of the patients endorsed slurred speech and incoordination since childhood. At time of referral, all presented with varying severity the following: ataxic dysarthria, gait ataxia, history of falls, tremor, proximal weakness (usually involving triceps and iliopsoas), dysphagia, jerky saccades. Mood disorders, attentional difficulties and impulsivity were also present. Cognitive impairment was not predominant. Uncommon symptoms were resting tremor, cortical signs, peripheral neuropathy, and slow saccades. The most common misdiagnosis were neuromuscular disorders. Cerebellar atrophy and family history were present in 50% of the cases.

Conclusions: LOTS is a rare disease due to the accumulation of gangliosides in the brain. Typically, it presents with cerebellar ataxia, proximal weakness, peripheral neuropathy, and psychiatric symptoms. Misdiagnosis with neuromuscular or psychiatric disorders is frequent. Our cohort pinpoints tips that may aid in earlier diagnosis. The characteristic and early speech impairment differentiates it from neuromuscular disorders. Weakness usually involves triceps, and iliopsoas. History of fall can challenge the diagnosis of a pure psychiatric disease, while prominent psychiatric features can help differentiate from other cerebellar ataxias. Those tips can facilitate an earlier diagnosis of a rare and complex condition.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/diagnostic-tips-from-a-case-series-of-patients-with-late-onset-tay-sachs-disease/