INTRODUCTION: GM2-Gangliosidosis are lysosomal storage disorders characterized by a deficiency of the enzyme β-hexosaminidase(s). They include Tay-Sachs (TS) and Sandhoff disease (SD), that are caused by mutations in HEXA and HEXB genes respectively.

OBJECTIVES: To compare the symptomatology of infantile forms of TS (iTS) and SD (iSD) using the GM2 Disease Registry (GM2DR) that was created by Cure & Action for Tay Sachs Foundation and Acción y Cura para Tay-Sachs.

METHODS: The associations among the different forms were assessed using Chi-2/Fisher exact tests.

RESULTS: In February 2023, 109 patients with an infantile form were enrolled in the registry: 30 with iSD and 79 with iTS. iSD experienced on average 9.2(SD:2.8) symptoms and 8.9(3.1) for iTS. The most common symptoms for iSD were the inability to communicate verbally and to sit unaided (93.3%), while for iTS, there were the inability to communicate verbally and the startle reflex (88.6%). Both diseases were similar in terms of symptomatology, except for startle reflex, which was more prevalent among iTS (88.6% vs. 70.0%,p=0.04).

The iTS includes the B1 variant (B1iTS) and the classical infantile (ciTS) which are different in terms of disease onset and progression. Symptoms are similar in iSD and ciTS, except for startle reflex (70.0% vs. 93.4% respectively, p<0.01). Several differences were observed among B1iTS and iSD with higher prevalence of assisted feeding (73.3% vs. 33.3%,p=0.01), inability to communicate verbally (93.3% vs. 61.1%,p<0.01), inability to sit unaided (93.3% vs. 50.0%,p<0.01) and absence of mobility (90.0% vs. 55.6%,p=0.01) in iSD compared to B1iTS.

CONCLUSIONS: The clinical course of iSD and iTS are considered alike. Our results confirmed that, in terms of symptoms, iSD and ciTS are similar. Nevertheless, we highlighted symptoms specificities for B1iTS compared to iSD and ciTS, which reinforce the need to recognize B1iTS as a distinguishable form of iTS.