title: Long-term hematological, visceral, and growth outcomes in children with Gaucher disease type 3 treated with imiglucerase in the International Collaborative Gaucher Group Gaucher Registry.
abstract: In Gaucher disease (GD), deficiency of lysosomal acid β-glucosidase results in a broad phenotypic spectrum that is classified into three types based on the absence (type 1 [GD1]) or presence and severity of primary central nervous system involvement (type 2 [GD2], the fulminant neuronopathic form, and type 3 [GD3], the milder chronic neuronopathic form). Enzyme replacement therapy (ERT) with imiglucerase ameliorates and prevents hematological and visceral manifestations in GD1, but data in GD3 are limited to small, single-center series. The effects of imiglucerase ERT on hematological, visceral and growth outcomes (note: ERT is not expected to directly impact neurologic outcomes) were evaluated during the first 5years of treatment in 253 children and adolescents (<18years of age) with GD3 enrolled in the International Collaborative Gaucher Group (ICGG) Gaucher Registry. The vast majority of GBA mutations in this diverse global population consisted of only 2 mutations: L444P (77%) and D409H (7%). At baseline, GD3 patients exhibited early onset of severe hematological and visceral disease and growth failure. During the first year of imiglucerase treatment, hemoglobin levels and platelet counts increased and liver and spleen volumes decreased, leading to marked decreases in the number of patients with moderate or severe anemia, thrombocytopenia, and hepatosplenomegaly. These improvements were maintained through Year 5. There was also acceleration in linear growth as evidenced by increasing height Z-scores. Despite devastating disease at baseline, the probability of surviving for at least 5years after starting imiglucerase was 92%. In this large, multinational cohort of pediatric GD3 patients, imiglucerase ERT provided a life-saving and life-prolonging benefit for patients with GD3, suggesting that, with proper treatment, many such severely affected patients can lead productive lives and contribute to society.
authors.affiliation: Pediatric Hospital of Cairo University, Cairo, Egypt.
authors.forename: Amal
authors.initials: A
authors.lastname: El-Beshlawy
authors.affiliation: Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Tylki-Szymanska
authors.affiliation: Great Ormond Street Children's Hospital NHS Foundation Trust, London, UK.
authors.forename: Ashok
authors.initials: A
authors.lastname: Vellodi
authors.affiliation: Referral Center for Lysosomal Diseases, University Hospital Paris Nord-Val de Seine Assistance Publique-Hôpitaux de Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Belmatoug
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Grabowski
authors.affiliation: New York University School of Medicine, New York, USA.
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Kolodny
authors.affiliation: Biostatistics/Epidemiology, Sanofi Genzyme, Cambridge, MA, USA.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Batista
authors.affiliation: Editas Medicine, Cambridge, MA, USA.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Cox
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA. Electronic address: pramod.mistry@yale.edu.
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Mistry
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000145:classification / Q000188:drug therapy* / Q000235:genetics; D005962:Glucosylceramidase / Q000235:genetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009154:Mutation; D012042:Registries; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005962:Glucosylceramidase; C090568:imiglucerase
keywords: Anemia; Enzyme replacement therapy; Gaucher disease type 3; Growth; Hepatosplenomegaly; Imiglucerase; Registry; Thrombocytopenia