title: Long-term efficacy of miglustat in paediatric patients with Niemann-Pick disease type C.
abstract: Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease characterized by progressive neurological manifestations. Oral miglustat was first approved for the treatment of children and adults with NP-C in Europe in 2009. There are still relatively few published data on the long-term efficacy and safety of miglustat in patients with NP-C in clinical practice. We report the effects of up to 6 years of treatment with miglustat 100 mg t.i.d. in five children. Overall, 3/5 patients displayed progressive dysphagia before starting miglustat, and 4/5 showed marked cognitive and/or motor impairment. The mean age at treatment start was 11.6 years, and the median (range) duration of therapy so far is 4 (4.1 to 6.1) years. No treatment dose alterations were required, but therapy was interrupted for 1-3 months at least once in all patients due to supply issues. Swallowing function was stabilised during miglustat therapy, with no significant increase in Han dysphagia scale or aspiration-penetration index scores among four evaluable patients (p > 0.05). Scores on the mini-mental state examination indicated an improvement in cognitive function during the first 3-6 months of miglustat therapy, followed by stabilisation up to 5 years. Ambulatory function remained stable for at least the first 2 years of treatment in most patients, but there was a trend towards deterioration thereafter, possibly related to treatment interruptions. The safety/tolerability profile of miglustat was similar to previous clinical studies, although reports of gastrointestinal disturbances were rare. Overall, miglustat appeared to stabilise key parameters of neurological disease progression.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Y H
authors.initials: YH
authors.lastname: Chien
authors.forename: S F
authors.initials: SF
authors.lastname: Peng
authors.forename: C C
authors.initials: CC
authors.lastname: Yang
authors.forename: N C
authors.initials: NC
authors.lastname: Lee
authors.forename: L K
authors.initials: LK
authors.lastname: Tsai
authors.forename: A C
authors.initials: AC
authors.lastname: Huang
authors.forename: S C
authors.initials: SC
authors.lastname: Su
authors.forename: C C
authors.initials: CC
authors.lastname: Tseng
authors.forename: W L
authors.initials: WL
authors.lastname: Hwu
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects; D003679:Deglutition / Q000187:drug effects; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000188:drug therapy; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy*; D013995:Time; D016896:Treatment Outcome
chemical_list: D017485:1-Deoxynojirimycin; C059896:miglustat