What is Niemann-Pick Disease?

by

National Niemann-Pick Disease Foundation

Niemann-Pick Disease ("Niemann-Pick") is actually a term for a group of diseases which affect metabolism and whihc are caused by specific genetic mutations. The three most commonly recognized forms of the disease are Type A, B and C.

Types A and B Niemann-Pick are both caused by the deficiency of a specific enzyme activity, acid sphingomyelinase (ASM). This enzyme is ordinarily found in special compartments within cells called lysosomes and is required to metabolize a special lipid, called sphingomyelin. If ASM is absent or not functioning properly, this lipid cannot be metabolized properly and is accumulated within the cell, eventually causing cell death and the malfunction of major organ systems.

Types A and B are both caused by the same enzymatic deficiency and there is a growing concensus that the two forms represent opposite ends of a continuous scale. People with Type A generally have little or no ASM production (less than 1% of normal) while those with Type B have approximately 10% of the normal level of ASM.

While both Type A and B hav ASM activity that is significantly lower than normal, 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 or 3 years of age. It is believed that the majority of Niemann-Pick cases are Type A.

In contrast, patients with Type B generally have little or no neurologic involvement and may survive into late childhood or adulthood. Type B individuals usually have enlarged livers and spleens, and respiratory problems are common. The enlargement of organs and the respiratory problems both can cause cardiovascular stress and can lead to heart disease later in life.

Patients with intermediate ASM activity tend to have more neurological problems that Type B but fewer problems than Type A. Because there is not a precise correlation between ASM activity and neurological involvement, it is not possible to accurately predict the severity of the disease by enzyme testing.

Type C Niemann-Pick, although similar in name to Types A and B, is very different at the biochemical and genetic level. Patients are not able to metabolize cholesterol and other lipids properly within the cell. Consequently, excessive amounts of cholesterol accumulate with the liver and spleen and excessive amounts of other lipids accumulate in the brain.

Because the defect in metabolism in Type C occasionally leads to a secondary reduction in ASM activity in some cells, all three types were originally called Niemann-Pick Disease.

Type C Niemann-Pick has 300 to 400 cases diagnosed world wide. It is believed that the number of people affected is higher but it is often difficult for the correct diagnosis to be made. Niemann-Pick Type C has been initially diagnosed as a learning disability, mild retardation, "clumsiness", and delayed development of fine motor skills. Vertical gaze palsy (the inability to move the eyes up and down), enlarged liver, or enlarged spleen are strong indications that [Niemann-Pick Type C] should be considered.

There is considerable variation in when symptoms first appear adn in the progression of the disease. Symptoms may appear as early as a few months old or as late as adulthood. In most cases, neurological symptoms begin appearing between the ages of 4 and 10. Generally, the later the neurological symptoms begin, the slower the progression of the disease.

Type C is always fatal. The vast majority of children die before age 20 (and many die before the age of 10). Late onset of symptoms can lead to longer life spans but it is extremely rare for any person to reach 40.

In the past, other types of Niemann-Pick were identified. The older forms include:

Niemann-Pick affects all segments of the population with cases reported from North America, South America, Europe, Africa, Asia, and Australia. However a higher incidence rate has been found in certain populations:

Pick's Disease is sometimes confused with Niemann-Pick but it is a differnt disease.

The National Niemann-Pick Disease Foundation home page is at www.nnpdf.org.
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