This section is intended for healthcare professionals outside of the US only. If you are a patient or a carer, please click here for further information.

Pathophysiology of Niemann-Pick type C disease

The primary biological defect in Niemann-Pick type C disease (NP-C) is impaired intracellular lipid transportation that leads to toxic accumulation of lysosomal lipids.1 In peripheral tissues such as the skin, it is predominantly unesterified cholesterol that accumulates.2 However, in the liver and spleen, several different types of lipid accumulate including unesterified cholesterol, glycosphingolipids, phospholipids and sphingomyelin.1 Glycosphingolipid accumulation primarily occurs in the central nervous system (CNS), including the brain.2

Figure 1: Cholesterol
transport in normal
and NP-C cells

In normal cells, low density lipoprotein (LDL) cholesterol enters cells via endocytosis at the LDL receptor and is delivered to the late-stage endosomes and lysosomes where it is hydrolyzed and released as free cholesterol (see Figure 1).1,3 Unesterified cholesterol is then transported to the plasma membrane and the endoplasmic reticulum (ER) for recycling within the cell.3

In NP-C, the LDL-cholesterol becomes trapped within the lysosomes, resulting in considerably reduced transport of unesterified cholesterol (see Figure 1).1,3,4 The end result is accumulation of lipids to toxic levels, which causes damage to cells and tissues, leading to the symptoms of NP-C.1



  1. Wraith JE, Imrie J. Understanding Niemann-Pick disease type C and its potential treatment. UK Blackwell Publishing, 2007.
  2. Patterson MC. A riddle wrapped in a mystery: understanding Niemann-Pick disease, type C Neurologist 2003; 9: 301-10.
  3. Vanier MT. Niemann-Pick disease type C Orphanet J Rare Dis 2010;5:16.
  4. Mukherjee S, Maxfield FR. Lipid and cholesterol trafficking in NPC Biochim Biophys Acta 2004; 1685: 28-37.