title: Substrate reduction therapy with miglustat for type 1 Gaucher disease: a retrospective analysis from a single institution.
abstract: BACKGROUND
  Gaucher disease (GD) is an infrequent progressive multisystem lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme, glucocerebrosidase. A retrospective, single-center analysis of the clinical experience concerning the use of miglustat (N-butyldeoxynojirimycin), an oral inhibitor of glucosylceramide synthase, in type 1 Gaucher disease (GD1) was conducted to evaluate the efficacy, adverse events (AE), and outcome of miglustat therapy.
  
  
  METHODS
  Six adult Caucasian patients with GD1 (two women and four men), aged 21-81 years (median age 59 years), were treated with miglustat between October 2005 and April 2011. All but one patient (83%) carried at least one allele with c.1226A>G (N370S) mutation in the GBA1 gene.
  
  
  RESULTS
  Weight loss, diarrhea, poor appetite, and tremor were frequently reported AE by the patients. All of them experienced at least 2 AE, and three patients (50%) experienced at least 4 AE. Only two out of six patients (33%) have used miglustat longer than 12 months, of which only one used it longer than 15 months.
  
  
  CONCLUSIONS
  The major obstacle to successful miglustat therapy in GD1 was the high proportion of patients discontinuing their treatment due to the AE and the worsened quality of life. Further efforts are needed to improve tolerability of miglustat and, in consequence, compliance of patients treated with this orphan drug.
authors.affiliation: Division of Hematology, Department of Medicine at Huddinge, Karolinska Institutet, and Hematology Center Karolinska, Karolinska University Hospital Huddinge, Stockholm, Sweden. maciej.machaczka@ki.se
authors.forename: Maciej
authors.initials: M
authors.lastname: Machaczka
authors.forename: Robert
authors.initials: R
authors.lastname: Hast
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.forename: Richard
authors.initials: R
authors.lastname: Lerner
authors.forename: Monika
authors.initials: M
authors.lastname: Klimkowska
authors.forename: Martin
authors.initials: M
authors.lastname: Engvall
authors.forename: Hans
authors.initials: H
authors.lastname: Hägglund
mesh_terms: D017485:1-Deoxynojirimycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat