Niemann-Pick disease type C

1. A D E W I J A Y A , M D
O C T O B E R 2 0 2 2
Niemann-Pick disease type C in Adults

2. Definition
 Niemann-Pick disease type C (NPC) is a
progressive and life limiting autosomal recessive
disorder caused by mutations in either the NPC1 or
NPC2 gene.
 Mutations in these genes are associated with
abnormal endosomal-lysosomal trafficking,
resulting in the accumulation of multiple lipids in
the lysosomes.
 Disease onset occurs through the lifespan, from
antenatal life to maturity

3. Epidemiology
 Rare, with an estimated incidence of 1 case per
100,000 live births.
 The disease is pan-ethnic, with at least 95% of all
disease due to mutations in the NPC1 gene and the
remainder in the NPC2 gene.

4. Classification
 1.visceral-neurodegenerative form
 Early-infantile (< 2 years)
 2.neurodegenerative form
 Late-infantile (2–6 years)
 Juvenile (6–15 years)
 3.Psychiatric-neurodegenerative form
 Adult (> 15 years)

5. Adult NPC Clinical Presentation
 Cognitive decline, dementia, learning disability
 Psychiatric signs: Schizophrenia (psychosis),
depression.
 Clumsiness, progressive motor symptoms, tremor,
ataxia, dystonia/dyskinesia, dysarthria, dysphagia
 Vertical supranuclear gaze palsy

6. Differential diagnosis
 Huntington disease
 Wilson disease
 Cerebrotendinous xanthomatosis
 GM1 or GM2 gangliosidoses
 Friedreich Ataxia
NPC  no peripheral neuropathy and normal brain
MRI other than atrophy

8. Assestment

9. Management
 Multidisciplinary approach
 Miglustat, a substrate reduction therapy, is the only
licensed disease modifying medicine in the European
Union for the treatment of neurological
manifestations of patients with NPC disease. In some
patients, miglustat has been shown to halt or
attenuate disease progression

10. Summary
 Lysosomal storage disease
 progressive and life limiting autosomal recessive
disorder caused by mutations in either the NPC1 or
NPC2 gene
 Rare
 Neuropsychiatric sumptoms
 Multidisciplinary approach
 miglustat

11. THANK YOU