Niemann–Pick disease is a group of severe inherited metabolic disorders, in which sphingomyelin accumulates in lysosomes in cells (the lysosomes normally degrade material that comes from out of cells). These disorders involve the dysfunctional metabolism of sphingolipids, which are fats found in cell membranes. They can be considered as a kind of sphingolipidosis, which is included in the larger family of lysosomal storage diseases. Signs and symptoms
Symptoms are related to the organs in which sphingomyelin accumulates. Enlargement of the liver and spleen (hepatosplenomegaly) may cause reduced appetite, abdominal distension, and pain. Enlargement of the spleen (splenomegaly) may also cause low levels of platelets in the blood (thrombocytopenia).Accumulation of sphingomyelin in the central nervous system (including the cerebellum) results in unsteady gait (ataxia), slurring of speech (dysarthria), and difficulty swallowing (dysphagia). Basal ganglia dysfunction causes abnormal posturing of the limbs, trunk, and face (dystonia). Upper brainstem disease results in impaired voluntary rapid eye movements (supranuclear gaze palsy). More widespread disease involving the cerebral cortex and subcortical structures causes gradual loss of intellectual abilities, causing dementia and seizures.Bones also may be affected, with the disease causing enlarged bone marrow cavities, thinned cortical bone, or a distortion of the hip bone called coxa vara. Sleep-related disorders also occur with the condition, such as sleep inversion, sleepiness during the day and wakefulness at night. Gelastic cataplexy, the sudden loss of muscle tone when the affected patient laughs, is also seen. Causes
Mutations in the SMPD1 gene cause Niemann–Pick disease types A and B.
In a longitudinal natural history study, nearly 20% of the patients died. For those classified into type C, they may have mild hepatosplenomegaly, but their central nervous system is profoundly affected. Niemann–Pick disease, SMPD1-associated, which includes types A and BNiemann–Pick disease type A: classic infantile
Niemann–Pick disease type B: visceralNiemann–Pick disease, type C: subacute/juvenile, includes types C1 (95% of type C) and C2. Type C is the most common form of the disease Type C2 is a rare form of the disease.Niemann–Pick disease type D (or Nova Scotia form) is now believed to be the same condition as Niemann–Pick disease type C. Two poorly characterized forms of Niemann–Pick disease have also been described as types E and F.

Treatment
No specific treatment is known for type A, but symptoms are treated.In adult patients with type B, physicians try to keep cholesterol levels down to normal levels. If statins are used, they monitor liver function. If the spleen is enlarged and platelet levels low, acute episodes of bleeding may require transfusions of blood products. If they have symptoms of interstitial lung disease, they may need oxygen.Anecdotally, organ transplant has been attempted with limited success. Future prospects include enzyme replacement and gene therapy. Bone marrow transplant has been tried for type B.In January 2009, Actelion announced the drug miglustat (Zavesca) had been approved in the European Union for the treatment of progressive neurological manifestations in adult patients and pediatric patients with NPC. The drug is available to patients in the United States on an experimental basis.