The Natural History of Late Onset Tay-Sachs Disease (P01.243)

Objective: To investigate whether late onset Tay-Sachs (LOTS) Disease phenotypes (juvenile and adult) overlap and whether LOTS can be better characterized. Background LOTS has a more chronic course than infantile Tay-Sachs disease and is divided into juvenile and adult phenotypes. Design/Methods: We reviewed retrospective surveys and performed prospective examinations using a brief ataxia rating scale. Results: Retrospective data from 55 LOTS patients (45 adult, 10 juvenile), showed a heterogeneous population with overlap in age of onset. Median onset in adults was 10 years (range 1 to 40) and in juveniles 2 years (range 1 to 4). Median progression from first symptom to becoming wheelchair-bound was 22 (adult) and 3.75 years (juvenile). Among both juvenile and adult LOTS the most common presenting symptoms were gait and speech abnormalities. Forty-five percent presented with gait difficulties as their first symptom (21/45 adult, age range 3 to 40 years; 4/10 juvenile, age range 1 to 4 years). Eighteen percent presented with speech difficulties (9/45 adult, age range 3 to 30 years; 2/10 juvenile, age range 1 to 1.5 years). Fifteen percent had motor problems without speech difficulties (8/45 adult, age range 7 to 40 years; 2/10 juvenile, age range 1.5 to 1.8 years). Prospective data from ten LOTS patients showed 80% (8/10) had muscle weakness and cerebellar dysfunction (range of onset 24 to 64 years) and 20% had selective lower motor neuron weakness with no cerebellar dysfunction (ages of onset 23 and 25 years), confirming the distribution and/or variation in phenotype of our retrospective cohort. Conclusions: Our studies confirm an overlap in age of first symptoms among juvenile and adult LOTS and consistent variation in phenotypes in both retrospective and prospective cohorts, with absence of cerebellar findings in 15 to 20% of LOTS patients. This research highlights the need for a better understanding of the natural history of LOTS. Supported by: National Tay-Sachs & Allied Disease Association. Disclosure: Dr. Yerramilli-Rao has nothing to disclose. Dr. Giannikopoulos has nothing to disclose. Dr. Kublis has nothing to disclose. Dr. Pan has nothing to disclose. Dr. Eichler has nothing to disclose.