EXPERIENCE OF MIGLUSTAT THERAPY IN PEDIATRIC PATIENTS WITH
NIEMANN-PICK TYPE C DISEASE
2Neuropediatrics Unit, Centro Hospitalar Universitário De Santo António, Portugal
Background: Niemann-Pick disease type C (NP-C) is a neurodegenerative lysosomal lipid storage disorder. Different clinical forms have been defined based on patient age at onset: early infantile (EI), late-infantile (Li), juvenile and adult. To date, miglustat is the only treatment specifically approved in the European Union for the treatment of progressive neurological manifestations in patients with NP-C.
Methods:Retrospective, descriptive study by reviewing the medical records of all NP-C patients treated with miglustat at our center.
Results:Six patients (4 male; 2 female) were included: 1 EI, 3 Li (case 2-4) and 2 juvenile forms (case 5-6). All had NPC1 pathogenic variants.
EI patient had severe hypotonia and hepatosplenomegaly; Li manifestations included slow motor function, ataxia, speech delay, and dystonia. Juvenile forms had praxis disorders, cerebello-dystonic syndrome, cognitive decline, and swallowing disorder. Vertical gaze palsy was universal. Cases 1-5 required a gastrostomy for dysphagia and feeding difficulties.
Regarding treatment: patient 1 began therapy 14 months after disease onset and was treated for 12 months (deceased). The median interval between onset and treatment was 3 years in Li, with a mean duration of 38.7 months and a current mean 5-domain NPC score of 20. In juvenile forms, case 5 has died; case 6 was diagnosed after her sister and begun therapy with an NPC score of 2. She has been treated for 30 months with a current NPC score of 3.
Discussion:NP-C diagnosis is often delayed due to the heterogeneous presentation and early non-specific symptoms.
Miglustat affects the disease hystory by stabilizing or delaying the neurological progression. The progression rate is faster in early presentations, potentially with a minor impact of miglustat, particularly when treatment is started in a more advanced phase.
Accordingly, our patients with later presentations and smaller interval between onset and treatment had a better response to therapy.
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