What is Niemann-Pick type C disease?

In Niemann-Pick type C disease (NP-C) the normal movement of fatty molecules (lipids) within cells is disrupted. Instead of being recycled or reused, these fatty molecules (particularly cholesterol and glycosphingolipids), which play a very important role in the structure and function of all cells, build up in various parts of the body, including the brain, liver and spleen.^1,2 Eventually, toxic levels of these fatty molecules are reached, causing cell damage, especially in the brain.^1,3

NP-C is an inherited disorder caused by mutations, or changes, in one of two genes (known as NPC1 and NPC2) that each produce a protein, called the gene product.⁴ Although the function of these gene products is not fully understood they play a very important role in the movement and recycling of fatty molecules within cells.^1,3 When the NPC1 or NPC2 gene is mutated the gene product does not function properly causing the fatty molecules to become trapped and thus build up in cells.

The build up of fatty molecules in the brain damages nerve cells (neurons) causing them to change shape, and grow abnormally. These changes lead to the characteristic neurological symptoms seen in NP-C.¹ The accumulation of fatty molecules also leads to the abnormal enlargement of the liver and/or spleen that often occurs in infants with NP-C.¹

References

1. Wraith JE, Imrie J. Understanding Niemann-Pick disease type C and its potential treatment. UK Blackwell Publishing, 2007.
2. Walkley SU, Suzuki K. Consequences of NPC1 and NPC2 loss of function in mammalian neurons. Biochim Biophys Acta 2004; 1685: 48-62.
3. Patterson MC. A riddle wrapped in a mystery: understanding Niemann-Pick disease, type C. Neurologist 2003; 9: 301-10.
4. Patterson MC. Niemann-Pick disease Type C. Gene Reviews 2007a (updated 9 July). Accessible at: www.geneclinics.org. Accessed October 2008.