title: Initiation and discontinuation of substrate inhibitor treatment in patients with Niemann-Pick type C disease.
abstract: Niemann-Pick type C disease (NP-C) is a lysosomal storage disorder characterized by a progressive neurological deterioration. Different clinical forms have been defined based on patient age at neurological symptoms onset: perinatal, early infantile (EI), late infantile (LI), juvenile and adult. There is no curative treatment for NP-C. Miglustat is the first effective therapy for the neurological manifestations of NP-C patients, as it can slow down the progression of the disease. Our aim is to establish recommendations on the initiation and discontinuations with miglustat therapy based on the modified disability scale scores and describe therapeutic options to prevent treatment-related adverse effects. Four patients with different clinical forms of NP-C are reported. The modified disability scale was applied at baseline and treatment on follow up. Treatment with miglustat was initiated in patient 1 (EI form) at onset of delayed speech. Patient 2 (LI form) who started miglustat therapy in the advanced stage of the disease, died 2 years thereafter. Patient 3 (juvenile form) started treatment with miglustat at diagnosis and remains stable at four years on follow up. Patient 4, asymptomatic, is not currently treated. Miglustat has demonstrated efficacy to slow down the neurological impairment in NP-C patients assessed by the modified disability scale. Miglustat should be initiated at the onset of the first neurological symptoms. Disability scores above 20 reflect an advanced neurological impairment of the disease and miglustat therapy should be discontinued or not initiated. The gastrointestinal adverse effects can be prevented by dose titration and dietary modifications.
authors: Department of Pediatric Neurology, Hospital de Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.
authors: María Socorro
authors: MS
authors: Pérez-Poyato
authors: M Mar O'Callaghan
authors: MM
authors: Gordo
authors: Mercé Pineda
authors: MP
authors: Marfa
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D004185:Disability Evaluation; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins; D007805:Language Development Disorders / Q000188:drug therapy / Q000523:psychology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D009154:Mutation; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology / Q000523:psychology
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D017485:1-Deoxynojirimycin; C059896:miglustat; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase