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

• Published in: Molecular genetics & genomic medicine 2020-10, Vol.8 (10), p.e1371-n/a
• Main Authors: Fischetto, Rita, Palladino, Valentina, Mancardi, Maria M., Giacomini, Thea, Palladino, Stefano, Gaeta, Alberto, Di Rocco, Maja, Zampini, Lucia, Lassandro, Giuseppe, Favia, Vito, Tripaldi, Maria E., Strisciuglio, Pietro, Romano, Alfonso, Severino, Mariasavina, Morrone, Amelia, Giordano, Paola
• Format: Article
• Language: English
• Subjects: Abdomen; Age; Alkylation; Central nervous system; Ceramide glucosyltransferase; Clinical Report; Clinical Reports; Cognitive ability; Convulsions & seizures; Drug dosages; Dysarthria; Enzymes; Gait; Galactosidase; Ganglioside GM1; Gangliosidosis; Glycoconjugates; GM1 gangliosidosis; Health services; Intellectual disabilities; Lysosomal storage diseases; Metabolic disorders; Miglustat; Mutation; Organs; Patients; pediatric; Pediatrics; Reduction; Strabismus; Substrates; Therapy; Vertebrae; β-Galactosidase
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.1371

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. In GM1 gangliosidosis the lack of function of β‐galactosidase results in an accumulation of GM1 gangliosides and related glycoconjugates in visceral organs, especially 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. 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. This treatment was safe and relatively well tolerated by all patients, with stabilization and/or slowing down of the neurological progression in three subjects.