Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience

Mol Genet Genomic Med. 2020 Oct;8(10):e1371. doi: 10.1002/mgg3.1371. Epub 2020 Aug 11.

Abstract

Background: In GM1 gangliosidosis the lack of function of β-galactosidase results in an accumulation of GM1 ganglioside and related glycoconjugates in visceral organs, and particularly in the central nervous system, leading to severe disability and premature death. In the type 2 form of the disease, early intervention would be important to avoid precocious complications. To date, there are no effective therapeutic options in preventing progressive neurological deterioration. Substrate reduction therapy with Miglustat, a N-alkylated sugar that inhibits the enzyme glucosylceramide synthase, has been proposed for the treatment of several lysosomal storage disorders such as Gaucher type 1 and Niemann Pick Type C diseases. However, data on Miglustat therapy in patients with GM1 gangliosidosis are still scarce.

Methods: We report here the results of Miglustat administration in four Italian children (average age: 55 months, range 20-125) affected by GM1 gangliosidosis type 2 treated in three different Italian pediatric hospitals specialized in metabolic diseases.

Conclusion: This treatment was safe and relatively well tolerated by all patients, with stabilization and/or slowing down of the neurological progression in three subjects.

Keywords: GM1 gangliosidosis; Miglustat; pediatric.

Publication types

  • Case Reports
  • Multicenter Study

MeSH terms

  • 1-Deoxynojirimycin / adverse effects
  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / pharmacology
  • 1-Deoxynojirimycin / therapeutic use
  • Adolescent
  • Central Nervous System / diagnostic imaging
  • Central Nervous System / drug effects
  • Child
  • Child, Preschool
  • Drug Tolerance
  • Female
  • Gangliosidosis, GM1 / drug therapy*
  • Glucosyltransferases / antagonists & inhibitors
  • Glucosyltransferases / metabolism
  • Glycoside Hydrolase Inhibitors / adverse effects
  • Glycoside Hydrolase Inhibitors / pharmacology
  • Glycoside Hydrolase Inhibitors / therapeutic use*
  • Humans
  • Infant
  • Male

Substances

  • Glycoside Hydrolase Inhibitors
  • 1-Deoxynojirimycin
  • miglustat
  • Glucosyltransferases
  • ceramide glucosyltransferase