Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience
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...
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doaj-8cb14bc6ee3e49df80c9e25b779f42e32020-11-25T03:41:50ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-10-01810n/an/a10.1002/mgg3.1371Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experienceRita Fischetto0Valentina Palladino1Maria M. Mancardi2Thea Giacomini3Stefano Palladino4Alberto Gaeta5Maja Di Rocco6Lucia Zampini7Giuseppe Lassandro8Vito Favia9Maria E. Tripaldi10Pietro Strisciuglio11Alfonso Romano12Mariasavina Severino13Amelia Morrone14Paola Giordano15Clinical Genetics Unit Department of Pediatric Medicine Giovanni XXIII Children's Hospital Bari ItalyDepartment of Biomedical Science and Human Oncology Pediatric Unit University of Bari “Aldo Moro” Bari ItalyUnit of Child Neuropsychiatry, Clinical and Surgical Neurosciences Department IRCCS Institute Giannina Gaslini Genoa ItalyUnit of Child Neuropsychiatry, Clinical and Surgical Neurosciences Department IRCCS Institute Giannina Gaslini Genoa ItalyRadiology Unit Pediatric Hospital Giovanni XXIII Bari ItalyRadiology Unit Pediatric Hospital Giovanni XXIII Bari ItalyUnit of Rare Diseases IRCCS Institute Giannina Gaslini Genoa ItalyDepartment of Clinical Sciences Division of Pediatrics Polytechnic University of MarcheOspedaliRiunitiPresidio Salesi Ancona ItalyDepartment of Biomedical Science and Human Oncology Pediatric Unit University of Bari “Aldo Moro” Bari ItalyClinical Genetics Unit Department of Pediatric Medicine Giovanni XXIII Children's Hospital Bari ItalyDepartment of Biomedical Science and Human Oncology Pediatric Unit University of Bari “Aldo Moro” Bari ItalyDepartment of Medical Translational Sciences Section of Pediatrics University Federico II Naples Napoli ItalyDepartment of Medical Translational Sciences Section of Pediatrics University Federico II Naples Napoli ItalyNeuroradiology Unit IRCCS Institute Giannina Gaslini Genoa ItalyPaediatric Neurology Unit and Laboratories Neuroscience Department Meyer Children's Hospital Florence ItalyDepartment of Biomedical Science and Human Oncology Pediatric Unit University of Bari “Aldo Moro” Bari ItalyAbstract 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.https://doi.org/10.1002/mgg3.1371GM1 gangliosidosisMiglustatpediatric |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 GM1 gangliosidosis Miglustat pediatric |
author_facet |
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 |
author_sort |
Rita Fischetto |
title |
Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience |
title_short |
Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience |
title_full |
Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience |
title_fullStr |
Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience |
title_full_unstemmed |
Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience |
title_sort |
substrate reduction therapy with miglustat in pediatric patients with gm1 type 2 gangliosidosis delays neurological involvement: a multicenter experience |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2020-10-01 |
description |
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. |
topic |
GM1 gangliosidosis Miglustat pediatric |
url |
https://doi.org/10.1002/mgg3.1371 |
work_keys_str_mv |
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