Niemann-Pick type C as a cause of progressive intellectual and neurological deterioration in childhood

Dev Med Child Neurol. 2017 Sep;59(9):965-972. doi: 10.1111/dmcn.13476. Epub 2017 Jun 2.

Abstract

Aim: To describe the cases of Niemann-Pick type C (NP-C) disease in a United Kingdom epidemiological study of progressive intellectual and neurological deterioration in childhood.

Method: Paediatricians notified cases via the British Paediatric Surveillance Unit between 1997 and 2015.

Results: Fifty-three NP-C patients were identified: 29 females, 24 males. Fifteen cases had a systemic presentation (neonatal jaundice and/or hepatosplenomegaly). Thirty-eight had a neurological onset, the commonest presenting symptom being gait disturbance/ataxia (29 cases, 76%). Forty-nine cases eventually had neurological problems, the commonest were school/cognitive difficulties (40, 82%), seizures (33, 67%), dysphagia (20, 41%), dysarthria (18, 37%), cataplexy (17, 35%), and visual deterioration (8, 16%); their commonest abnormal physical signs were vertical supranuclear gaze palsy (35, 71%), hypotonia (19, 39%) and hepatosplenomegaly (19, 39%). The median diagnostic delay in the 38 neurological onset cases was 3 years (range 0.3-12.8). Confirmatory investigations included filipin staining of skin fibroblasts (42 cases), bone marrow examination in 30 (the last in 2011), and increasingly DNA studies, mutations in NP-C1 being found in 20 cases.

Interpretation: NP-C should be considered in children with progressive neurological deterioration. Subtle neurological problems combined with a history of prolonged neonatal jaundice and/or hepatosplenomegaly may provide early evidence of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives
  • 1-Deoxynojirimycin / therapeutic use
  • Adolescent
  • Adult
  • Age of Onset
  • Brain / diagnostic imaging
  • Child
  • Child, Preschool
  • Delayed Diagnosis
  • Disease Progression
  • Epidemiological Monitoring
  • Female
  • Follow-Up Studies
  • Glycoside Hydrolase Inhibitors / therapeutic use
  • Humans
  • Infant
  • Intellectual Disability / diagnosis
  • Intellectual Disability / epidemiology
  • Intellectual Disability / etiology*
  • Intellectual Disability / physiopathology
  • Male
  • Niemann-Pick Disease, Type C / complications*
  • Niemann-Pick Disease, Type C / epidemiology
  • Niemann-Pick Disease, Type C / physiopathology*
  • Niemann-Pick Disease, Type C / psychology
  • Prospective Studies
  • Time Factors
  • United Kingdom / epidemiology

Substances

  • Glycoside Hydrolase Inhibitors
  • 1-Deoxynojirimycin
  • miglustat