Niemann-Pick disease and platelet dysfunction

Niemann-Pick type C (NPC) diseases, caused by mutations in NPC1 or NPC2, are rare inherited disorders affecting cholesterol metabolism, and are characterised by progressive neurodegeneration and premature death. In some affected individuals, haematological defects such as thrombocytopenia (low platelet counts) and anaemia are also observed. Louwette et al. now characterise platelet abnormalities in three unrelated patients carrying NPC1 mutations, and in NPC1-depleted zebrafish embryos. In patients, platelets were present in normal numbers but showed functional impairments. Patients’ haematopoietic stem cells were defective in differentiation into megakaryocytes (platelet precursors), although red blood cells differentiated normally. Zebrafish embryos depleted for NPC1 showed abnormal numbers of thrombocytes and red blood cells, suggesting that the entire myeloid lineage was affected. How defects in lipid metabolism caused by NPC1 mutations lead to defects specifically in the myeloid lineage remains an open question.