Niemann-Pick disease type C
Citation, DOI & article data
Niemann-Pick disease type c (NPD-C or just 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.
NPD-C is inherited as an autosomal recessive disorder with an estimated minimal incidence of 1/120,000 live births 2.
NPD-C has a variable age of presentation, ranging for the neonatal period into adulthood.
- hepatobiliary signs and symptoms 2
- neonatal presentation: cholestatic liver failure
- infancy and childhood presentation: hepatosplenomegaly
- neurological signs and symptoms 2
- neonatal and infant presentation: delayed development milestones
- childhood presentation: ataxia, falls, supranuclear vertical gaze palsy, cognitive impairment (e.g. poor school performance)
- adolescent and adult presentation: ataxia, supranuclear vertical gaze palsy, psychiatric illnesses, cognitive impairment
Radiographic features are limited, and MRI is the modality of choice.
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 the 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 addresses individual symptoms (e.g. antiepileptics for seizure control).
Although invariable NPD-C 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 features (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.
- 1. Rosenberg RN. The Molecular and Genetic Basis of Neurologic and Psychiatric Disease. Lippincott Williams & Wilkins. (2008) ISBN:0781769566. Read it at Google Books - Find it at Amazon
- 2. Vanier MT. Niemann-Pick disease type C. Orphanet J Rare Dis. 2010;5 (1): 16. doi:10.1186/1750-1172-5-16 - Free text at pubmed - Pubmed citation
- 3. Huang JY, Peng SF, Yang CC et-al. Neuroimaging findings in a brain with Niemann-Pick type C disease. J. Formos. Med. Assoc. 2011;110 (8): 537-42. doi:10.1016/S0929-6646(11)60080-6 - Pubmed citation
- 4. Walterfang M, Patenaude B, Abel LA et-al. Subcortical volumetric reductions in adult Niemann-Pick disease type C: a cross-sectional study. AJNR Am J Neuroradiol. 2013;34 (7): 1334-40. doi:10.3174/ajnr.A3356 - Pubmed citation
- 5. Walterfang M, Macfarlane MD, Looi JC et-al. Pontine-to-midbrain ratio indexes ocular-motor function and illness stage in adult Niemann-Pick disease type C. Eur. J. Neurol. 2012;19 (3): 462-7. doi:10.1111/j.1468-1331.2011.03545.x - Pubmed citation