Natural history of GM1 gangliosidosis-Retrospective cohort study of 61 French patients from 1998 to 2019

J Inherit Metab Dis. 2023 Sep;46(5):972-981. doi: 10.1002/jimd.12646. Epub 2023 Jul 11.

Abstract

GM1 gangliosidosis is a rare lysosomal storage disorder associated with β-galactosidase enzyme deficiency. There are three types of GM1 gangliosidosis based on age of symptom onset, which correlate with disease severity. In 2019, we performed a retrospective multicentric study including all patients diagnosed with GM1 gangliosidosis in France since 1998. We had access to data for 61 of the 88 patients diagnosed between 1998 and 2019. There were 41 patients with type 1 (symptom onset ≤6 months), 11 with type 2a (symptom onset from 7 months to 2 years), 5 with type 2b (symptom onset from 2 to 3 years), and 4 with type 3 (symptom onset >3 years). The estimated incidence in France was 1/210000. In patients with type 1, the first symptoms were hypotonia (26/41, 63%), dyspnea (7/41, 17%), and nystagmus (6/41, 15%), whereas in patients with type 2a, these were psychomotor regression (9/11, 82%) and seizures (3/11, 27%). In types 2b and 3, the initial symptoms were mild, such as speech difficulties, school difficulties, and progressive psychomotor regression. Hypotonia was observed in all patients, except type 3. The mean overall survival was 23 months (95% confidence interval [CI]: 7, 39) for type 1 and 9.1 years (95% CI: 4.5, 13.5) for type 2a. To the best of our knowledge, this is one of the largest historical cohorts reported, which provides important information on the evolution of all types of GM1 gangliosidosis. These data could be used as a historical cohort in studies assessing potential therapies for this rare genetic disease.

Keywords: GM1 gangliosidosis; central nervous system; lysosomal disorder; neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gangliosidosis, GM1* / diagnosis
  • Gangliosidosis, GM1* / epidemiology
  • Gangliosidosis, GM1* / genetics
  • Humans
  • Lysosomal Storage Diseases*
  • Muscle Hypotonia
  • Retrospective Studies
  • beta-Galactosidase

Substances

  • beta-Galactosidase