Niemann-Pick Disease Type C (NP-C) is a rare autosomal recessive neurodegenerative disease. It belongs to the group of lysosomal storage diseases and is characterized by a progressive course and in particular neuropsychiatric symptoms.
The disease is caused to 95% by a mutation of the NP-C1 gene and to 5% of the NP-C2 gene. The consequence is an impairment of intracellular lipid transport. Unestered cholesterol is stored in the lysosomes, resulting in intracellular accumulation and delayed sphingomyelin metabolism. The clinical symptoms are exceptionally heterogeneous and the possible manifestation age of the disease ranges from the perinatal period to adulthood.
Initial symptoms of NP-C disease in the perinatal period may be hepatosplenomegaly and prolonged cholestatic neonatal jaundice. Jaundice usually recovers spontaneously, but may also progress to fulminant liver failure. Even in early childhood, the disease can be noticed for the first time by hepatosplenomegaly. In addition, initial neurological symptoms may occur, in particular, delays in motor development or the loss of acquired motor abilities. Central hypotonia is also typical. In later childhood, delayed speech development, ataxia with falling inclination, and development of progressive dementia are at the forefront.
In up to 80% of patients, supranuclear vertical palsy (VSGP) can be observed, which can be considered as an early indication of a neurodegenerative process. Psychiatric symptoms such as acute psychosis with audiovisual hallucinations, bipolar maltreatment, or depression are most likely to be present at the onset of onset of adolescence.
The prognosis depends on the onset of the neurological symptoms, the earlier these occur the worse the prognosis.