Niemann-Pick disease type C

Niemann-Pick disease type c (NPC) is an autosomal recessive lysosomal storage disorder classed under Niemann-Pick disease on account of clinical similarities, namely hepatosplenomegaly and variable involvement of the central nervous system. 

Epidemiology

NPC is inherited as a autosomal recessive disorder with an estimated minimal incidence of 1/120 000 live births ². 

Clinical presentation

Niemann-Pick disease type C (NPC) has a variable age of presentation, ranging for the neonatal period into adulthood. 

• hepatobiliary signs / symptoms ² 
  • neonatal presentation: cholestatic liver failure
  • infancy and childhood presentation: hepatosplenomegaly
• neurological signs / symptoms ²
  • neonatal and infant presentation: delayed development milestones
  • childhood presentation: ataxia, falls, poor school performance
  • adolescent and adult prestenation: psychiatric illnesses, ataxia

Radiographic features

Radiographic features are limited, and MRI is the modality of choice. 

MRI

Reported abnormalities include:

• cerebral (particularly frontal lobe) and cerebellar atrophy ^2-3.
• white matter high T2 signal, particularly parieto-occipital periventricular regions ³
• deep grey matter and hippocampal atrophy (reported in adult onset patient) ⁴
• reduced midbrain to pons ratio (not as marked as in progressive supranuclear palsy (PSP)) ⁵

Treatment and prognosis

Unfortunately to date there is no disease modifying treatment available and management address individual symptoms (e.g. antiepileptics for seizure control). 

Although invariable NPC leads to premature death, in almost all cases before the age of 50 years of age, the rate of progression is highly variable.

Age of onset of systemic (e.g. hepatosplenomegaly) is not a good predictor, whereas the age at which neurological impairment becomes evident does correlate with survival: the earlier the onset of neurological signs and symptoms, the shorter the life expectancy ².