Niemann Pick Disease Type C
Niemann-Pick disease type C (NP-C) is a rare disorder affecting both the nervous system and internal organs. It is one of about 50 diseases caused by a lysosomal abnormality. The definition of NP-C has evolved over the years; it used to be related to the accumulation of any type of lipid (fats) but now it describes the accumulation of cholesterol and related lipids only.
NPC1 and NPC2 are the proteins that are involved in the intracellular processing of lipids. The exact functions of NPC1 and NPC2 proteins are not known but when these proteins are faulty due to the mutations in DNA, the lipids start accumulating in the late lysosomes.
The age of onset of NP-C is highly variable with some cases diagnosed at the time of birth to some in their 80s. NP-C is always fatal but the life expectancy of NP-C patients ranges from a few days to over half a century. NP-C is classified into early infantile, late infantile, juvenile, and adult form based on the age of onset.
The symptoms of NP-C are divided into 3 main categories visceral (related to organs of the body located in the chest and abdomen), neurological and psychiatric. The specific symptoms are:
Splenomegaly (enlargement of the spleen)
Hepatomegaly (enlargement of the liver)
Cholestatic jaundice (obstructive jaundice; when the liver cannot export a chemical called bilirubin) in newborns
Aspiration pneumonia (when food is breathed into the airways)
Mild thrombocytopenia (low blood platelet count)
Vertical supranuclear gaze palsy (inability to look in the vertical direction)
Gelastic cataplexy (sudden muscle weakness triggered by laughing)
Ataxia (a disorder that affects co-ordination, balance, and speech)
Dystonia (slow involuntary muscle contractions)
Dysarthria (speech disorder)
Dysphagia (swallowing difficulties)
Myoclonus (sudden muscle twitch)
Hypotonia (decreased muscle tone)
NP-C is difficult to diagnose and there is an approximate gap of 5-6 years in the appearance of symptoms and the diagnosis. Diagnosis involves physical examination, biomarkers tests, and genetic tests.
The coexistence of some of the above-mentioned symptoms is the first indication of the presence of NP-C. A genetic test can confirm the diagnosis of NP-C. Biomarkers are required for the evaluation of treatment. There is no specific biomarker for NP-C, rather a combination of different biomarkers such as filipin staining test, chitotriosidase, oxysterols, lysosphingolipids, and bile acids metabolites are used.
There is no cure and no FDA-approved drug for the treatment of NP-C. However, miglustat is approved in many countries due to its disease-modifying effects. It can slow down the progression of NP-C and increase life expectancy along with symptomatic relief. Physical exercise and nutritional changes increase the effects of miglustat therapy. Furthermore, antidepressants and cholesterol-lowering drugs have some symptomatic relief.
Other drugs such as cyclodextrins, vorinostat, acetylleucine, and arimoclomol, which are currently in trials, have the potential to be even more effective. Similarly, stem cell therapy and gene editing have the potential to treat NP-C but these techniques are still in early development and trials. Further research is needed to increase survival as well as improve the quality of life of the patients.