Niemann-Pick disease is caused by specific genetic mutations. The four forms of Niemann-Pick Disease are all characterized by an accumulation of sphingomyelin and cholesterol in cells, particularly in the cells of major organs, such as the liver and the spleen. The three most commonly recognized forms of the disease are Types A, B and C.

Alternative Names

Sphingomyelinase deficiency (type A Niemann-Pick disease)

Causes, incidence, and risk factors

All types of Niemann-Pick are genetic diseases that are inherited in an autosomal recessive manner. Types A and B Niemann-Pick are both caused by the deficiency of a specific enzyme activity, acid sphingomyelinase (ASM). If ASM is absent or not functioning properly, sphingomyelin cannot be metabolized properly and is accumulated within the cell, eventually causing cell death and the malfunction of major organ systems. Type C Niemann-Pick is very different from types A and B. Patients with Type C are not able to metabolize cholesterol and other lipids properly. Consequently, excessive amounts of cholesterol accumulate within the liver and spleen and excessive amounts of other lipids accumulate in the brain. The defect in metabolism occasionally leads to a secondary reduction in ASM activity in some cells. Type C Niemann-Pick disease has been reported in all ethnic groups. There is a higher than average prevalence of the disease in Puerto Ricans of Spanish descent. Type D Niemann-Pick has only been found in the French Canadian population of Yarmouth County, Nova Scotia and is now thought to be a variant of Type C. Geneological research indicates that Joseph Muise (c. 1679 - 1729) and Marie Amirault (1684 - c. 1735) are common ancestors to all Type D cases. This couple is the most likely origin for the Type D variant. Based on tissue and chemical changes similar to Type C, but with very late adult onset, a Type E Niemann-Pick has also been suggested. Pick's Disease is sometimes confused with Niemann-Pick but it is a different disease.

Signs and tests

Type A and B Niemann-Pick are diagnosed by measuring the ASM (acid sphingomyelinase) activity in white blood cells. The test can be performed after taking a small blood sample from suspected individuals. This test will be able to identify persons with the disease, but is unreliable in detecting persons who may be carriers. However, it is possible to diagnose Types A and B carriers by DNA testing because the gene containing the blueprint for ASM has been cloned and many of its mutations identified. Type C Niemann-Pick is initially diagnosed by taking skin biopsy, growing the cells in the laboratory, and then studying their ability to transport and store cholesterol. It is important that tests for both transport and storage be performed. Genetic testing is feasible following the discovery of 2 genes that cause Niemann-Pick type C disease. Additional tests might include:

Treatment

For Types A and B Niemann-Pick the ASM gene has been isolated and extensively studied. DNA testing and prenatal diagnosis is currently available. Research into treatments for Types A and B NPD has progressed rapidly since the early 1990's. Mount Sinai School of Medicine is conducting research on bone marrow transplantation, enzyme replacement therapy, and gene therapy. All of these therapies have had some success against Type B Niemann-Pick in a laboratory environment. Unfortunately, none of the potential therapies has been effective against Type A. For Type C Niemann-Pick, no specific treatment is available. A healthy, low-cholesterol diet is recommended. However research into low-cholesterol diets and cholesterol-lowering drugs do not indicate that these halt the progress of the disease or change cholesterol metabolism at the cellular level. Additionally, many Type C symptoms, such as cataplexy and seizures, can be controlled or tempered by drugs. The National Niemann-Pick Disease Foundation website has more in-depth reporting on the research into potential treatments.

Support groups

The National Niemann-Pick Disease Foundation 877-287-3672

Expectations (prognosis)

Although Types A and B are both caused by the same enzymatic deficiency, the clinical prognosis for these two groups of patients is very different. Type A Niemann-Pick is a severe neurologic disease, which generally leads to death by 2 to 3 years of age. In contrast, patients with Type B generally have little or no neurologic involvement and may survive into late childhood or adulthood. The underlying reason for this dramatic difference in the two forms of the disease is not really understood, and, at present, it is not possible to accurately predict the severity of the disease by enzyme testing. A child showing signs of Type C before one year of age may not live to school age. Children showing symptoms after entering school may live into their mid to late teens, with few surviving into their twenties.

Complications

Calling your health care provider

Call for an appointment with your health care provider and genetic counselor if you have a family history of this disorder and you plan to have children. Considering calling your health care provider if you have a child that has feeding problems, does not seem to be developing properly, or seems to be not gaining weight properly.

Prevention

All types of Niemann-Pick are autosomal recessive. This means that both parents carry one copy of the abnormal gene, without having any signs of the disease themselves. In this state the parents are commonly called carriers. When both parents are carriers, there is a 1 in 4 chance that a child will be affected with the disease and 1 in 2 chance that a child will be a carrier. Carrier detection testing for all families is not yet reliable. The mutations for Types A and B have been extensively studied, particularly among the Ashkenazi Jewish population, and DNA tests for these forms of Niemann-Pick are available. Mutations have been identified in the DNA of many patients with type C Niemann-Pick disease -- carrier detection may be possible. Antenatal diagnosis (diagnosis in the fetus) of NPD is available in a limited number of centers. Carrier detection is possible for other families only after their specific mutation is identified.