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

Molecular genetics & genomic medicine 2020 Oct

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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. 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. This treatment was safe and relatively well tolerated by all patients, with stabilization and/or slowing down of the neurological progression in three subjects. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

Citation

Rita Fischetto, Valentina Palladino, Maria M Mancardi, Thea Giacomini, Stefano Palladino, Alberto Gaeta, Maja Di Rocco, Lucia Zampini, Giuseppe Lassandro, Vito Favia, Maria E Tripaldi, Pietro Strisciuglio, Alfonso Romano, Mariasavina Severino, Amelia Morrone, Paola Giordano. Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience. Molecular genetics & genomic medicine. 2020 Oct;8(10):e1371