OBJECTIVES: This retrospective cohort study aimed to describe clinical characteristics among patients with and without GM2 gangliosidoses in the US.

METHODS: The Optum^® Market clarity database (linked claims and EHR) was used to identify patients with GM2 gangliosidoses (between 1-October-2015 and 30-September-2021) defined as those with ≥2 EHRs with a GM2-related ICD-10 code (E75.0/E75.00/E75.01/E75.02/E75.09) or one EHR and two claims with GM2-related ICD-10 codes on different days. Patients with GM2 gangliosidoses were matched 1:10 with a random sample of patients without GM2 gangliosidoses on age and gender. Clinical characteristics were assessed using ICD codes and natural language processing extracted terms from physician notes. Results were stratified by age groups (pediatric: 2 to <18 years; adult: ≥18 years).

RESULTS: Overall, 115 patients with GM2 gangliosidoses (pediatric: N=26, mean [SD] age: 5.1 [3.7] years; adult: N=89, 47.6 [17.1] years; mean (SD) baseline observability: 1,994 [1,348] days) were matched to 1,150 patients without GM2 gangliosidoses (pediatric: N=260; adult: N=890). At baseline, the most frequent manifestations among children with GM2 gangliosidoses were seizures/epilepsy (81%), aphagia/dysphagia (65%), developmental disorders (65%), ataxia (58%) and hypotonia (50%) and were ≥5 times more prevalent than in children without GM2 gangliosidoses. Depression was more prevalent among adults with GM2 gangliosidoses than in those without (57% vs. 45%), while anxiety prevalence was comparable between both groups (56% vs. 50%). Conversely, muscle weakness (52%), falls (51%), fractures (39%), ataxia (39%), urine incontinence (35%), aphagia/dysphagia (34%), altered mental status (29%), tremors (28%), speech disturbances (25%), bipolar disorder (19%), cognitive impairment (15%) and mania (11%) were ≥2 times more prevalent in adults with GM2 gangliosidoses than in those without.

CONCLUSIONS: Patients with GM2 gangliosidoses experience substantial clinical burden encompassing a wide range of manifestations. These findings highlight an urgent need for better diagnosis, disease-modifying treatments and comprehensive management strategies to address complex unmet needs of this population.