Splenomegaly and progressive neurologic involvement: Think about Niemann-Pick type C disease

Pediatr Int. 2024 Jan-Dec;66(1):e15832. doi: 10.1111/ped.15832.

Abstract

Background: Niemann-Pick type C (NPC) disease is a lysosomal storage disease with visceral organ involvement and neurological and psychiatric symptoms. This study presents the clinical and laboratory findings of NPC cases involving three novel variants.

Methods: The clinical and laboratory findings were reviewed retrospectively between February 2006 and December 2022.

Results: There were nine females and five males. The median age of diagnosis of the patients was 5 months (range: 1 month to 38 years). The clinical phenotypes of the patients were early infantile (n = 7), late infantile (n = 4), juvenile (n = 2), and adult (n = 1). The visceral findings were splenomegaly (100%), hepatomegaly (78.6%), neonatal jaundice (42.8%), and hepatic failure (14.3%). The neurological findings were developmental delay (71.4%), seizures (50%), vertical supranuclear gaze palsy (28.6%), ataxia (28.6%), dysarthria (28.6%), dysphagia (21.4%), dystonia (21.4%). Cataplexy (14.3%) and psychiatric manifestations (14.3%) were recorded in juvenile and adult-onset patients. Three novel variants were detected (p.Asn524LysfsTer39, p.Val1023Phe, and p.Asn906Tyr). Miglustat treatment was received by 64.3% of patients but had no clear effect on the disease course. The median duration of use was 3 years (with a range from 1-13 years). Miglustat's adverse effects were low platelet count (35.7%) and diarrhea (7.1%).

Conclusions: Niemann-Pick type C disease should be considered in the presence of visceral organ involvement and progressive neurological findings. It is essential to support the diagnosis with laboratory and genetic analysis.

Keywords: NPC; Niemann–Pick type C; miglustat; neurological involvement; splenomegaly.

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives
  • 1-Deoxynojirimycin / therapeutic use
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Humans
  • Infant
  • Male
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / etiology
  • Niemann-Pick Disease, Type C* / complications
  • Niemann-Pick Disease, Type C* / diagnosis
  • Phenotype
  • Retrospective Studies
  • Splenomegaly* / etiology
  • Young Adult

Substances

  • 1-Deoxynojirimycin