title: Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: a case series.
abstract: Niemann-Pick disease type C (NP-C) is an inherited neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Different clinical forms have been defined based on patient age at onset: perinatal, early-infantile (EI), late-infantile (Li), juvenile and adult. We evaluated the efficacy and tolerability of miglustat in 16 symptomatic NP-C patients, with comparative reference to one neurologically asymptomatic, untreated patient. All patients were categorized according to age at neurological disease onset, and were assessed using a standardized clinical assessment protocol: disability and cognitive function scales, positron emission tomography (PET), and biochemical markers. PET and disability scale evaluations indicated that cerebral hypometabolism and neurological symptoms were stabilized during treatment in juvenile-onset NP-C patients. EI and Li NP-C patients, who had higher disease severity at baseline (treatment start), showed increased disability scores and progressive cerebral hypometabolism during follow up. Similarly, while cognitive scale scores remained relatively stable in patients with juvenile NP-C, cognition deteriorated in EI and Li patients. Plasma chitotriosidase (ChT) activity was lower in the juvenile NP-C subgroup than in EI and Li patients, and generally increased in patients who discontinued treatment. Plasma CCL18/PARC and ChT activities indicated greater macrophagic activity in EI and Li patients versus juveniles. Miglustat was generally well tolerated; frequent adverse events included diarrhea and flatulence, which were managed effectively by dietary modification and loperamide. Overall, miglustat appeared to stabilize neurological status in juvenile-onset NP-C patients, but therapeutic benefits appeared smaller among younger patients who were at a more advanced stage of disease at baseline.
authors.affiliation: Department of Pediatric Neurology, Hospital Sant Joan de Déu, Barcelona, Spain. pineda@hsjdbcn.org
authors.forename: M
authors.initials: M
authors.lastname: Pineda
authors.forename: M S
authors.initials: MS
authors.lastname: Perez-Poyato
authors.forename: M
authors.initials: M
authors.lastname: O'Callaghan
authors.forename: M A
authors.initials: MA
authors.lastname: Vilaseca
authors.forename: M
authors.initials: M
authors.lastname: Pocovi
authors.forename: R
authors.initials: R
authors.lastname: Domingo
authors.forename: L Ruiz
authors.initials: LR
authors.lastname: Portal
authors.forename: A Verdú
authors.initials: AV
authors.lastname: Pérez
authors.forename: T
authors.initials: T
authors.lastname: Temudo
authors.forename: A
authors.initials: A
authors.lastname: Gaspar
authors.forename: J J Garcia
authors.initials: JJ
authors.lastname: Peñas
authors.forename: S
authors.initials: S
authors.lastname: Roldán
authors.forename: L Martín
authors.initials: LM
authors.lastname: Fumero
authors.forename: O Blanco
authors.initials: OB
authors.lastname: de la Barca
authors.forename: M T García
authors.initials: MT
authors.lastname: Silva
authors.forename: J
authors.initials: J
authors.lastname: Macías-Vidal
authors.forename: M J
authors.initials: MJ
authors.lastname: Coll
mesh_terms: D017485:1-Deoxynojirimycin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000188:drug therapy; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy*
chemical_list: D017485:1-Deoxynojirimycin; C059896:miglustat