Background: Tay Sachs (TS) is a rare neurodegenerative lysosomal storage disorder resulting from a mutation in the HEXA gene, which leads to accumulation of GM2 ganglioside in the brain. Patients can be diagnosed with adult (aTS), juvenile (jvTS), or infantile TS (iTS). Patients with iTS can be further categorized into classical infantile (ciTS) and late infantile or B1 variant (B1TS).
Objectives: The goal of the study is to characterize each of the TS variants and the iTS subpopulations using the GM2 Disease Registry (GM2DR).
Methods: The GM2DR is a multinational European registry established by the Cure & Action for Tay Sachs (CATS) Foundation and Acción y Cura para Tay-Sachs (ACTAYS), that has collected data from TS and Sandhoff patients since 2015. Data was self-reported from patients or caregivers via a web-based platform. Outcomes are here reported as means and standard deviations (SD) for continuous variables and as counts and proportions for categorical variables.
Results: As of April 2020, 85 patients with TS had been enrolled in the registry, among which 7 aTS, 12 jvTS and 66 iTS. More than half (51.5%) of the iTS, one third (33.3%) of the jvTS and 85.7% of the aTS are females. Children with iTS developed their first symptoms at the youngest age (mean±SD: 0.6±1.1y) and were diagnosed at 1.6±1.9y. Time from first symptoms to diagnosis was longer in jvTS and aTS patients: jvTS were diagnosed at 8.9±5.4y after experiencing first symptoms at 4.2±3.2y and aTS were diagnosed at 28.7±6.4y and showed first symptoms at 18.0±8.0y. Amongst the 46 patients who were still alive at the time of the study, the mean age was 5.3±3.4 for iTS, 18.2±7.5 for jvTS and 38.0±5.1 for aTS. Among the 39 deceased patients, 37 were iTS patients who died at an average age of 4.0±2.0y, and 2 were aTS deceased at 51.0±4.2y. With regards to the 2 iTS subpopulations, ciTS had their first symptoms at a younger age (0.3±0.6y) and were diagnosed at 0.8±0.7y, whilst B1iTS were diagnosed only at 3.7±2.5y despite having had developed their first symptoms at 1.5±1.2y. Among the deceased patients, 30 were ciTS who died at a mean age of 3.6±1.9y suggesting a faster progression of the disease when compared to the 7 B1iTS who had an average age at death of 7.3±3.1y.
Conclusions: Rare diseases are defined in Europe as those affecting less than 1 in 2000 people. The low prevalence is a barrier to effectively collect data. Disease registries such as the GM2DR are therefore crucial to the research of the longitudinal progression of rare diseases. Here, we further the understanding of the specificities of each of the TS variants, including the iTS subpopulations. Our results show clear differences not only across the three main variants but also between the two iTS subpopulations.