What Is Niemann-Pick Disease?

Niemann-Pick Disease ("Niemann-Pick") is actually a term for a group of diseases which affect metabolism and which are caused by specific genetic mutations. The three most commonly recognized forms of the disease are Types 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 have 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 leads to death by 2 to 4 years of age.

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 than 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. There are approximately 1,200 cases world wide with the majority being Type B or an intermediate form.

There are approximately 1,200 Type A or Type B cases diagnosed world wide with the majority being Type B.

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 within the liver and spleen and excessive amounts of other lipids accumulate in the brain. Type C causes a secondary reduction of ASM activity, which led all three types to be considered forms of the same disease.
[ Learn More ... about how cholesterol is metabolized in the cells. ]

There is considerable variation in when Type C symptoms first appear and in the progression of the disease. Symptoms may appear as early as a few months old or as late as adulthood. Vertical gaze palsy (the inability to move the eyes up and down), enlarged liver, enlarged spleen, or jaundice in young children are strong indications that NPC should be considered. It is common for only one or two symptoms to appear in the early stages of the disease.

In most cases, neurological symptoms begin appearing between the ages of 4 and 10. Generally, the later neurological symptoms begin, the slower the progression of the disease.

Type C Niemann-Pick has about 500 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. It is not uncommon for a family to spend several years seeking a diagnosis before Type C is identified.
[ Learn More ... a clinical and diagnostic review written for medical professionals. ]

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:

Type D Niemann-Pick was described in the French Canadian population of Yarmouth County, Nova Scotia. Geneological evidence indicates that Joseph Muise (c. 1679 - 1729) and Marie Amirault (1684 - c. 1735) are common ancestors to all of the Nova Scotia cases. This is now recognized as a variation of Type C.
Type E Niemann-Pick was described for cases of adults onset. This is now considered a variation of Type C where the metabolic processes are only partially disfunctional, slowing the onset and progression of symptoms.

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 of has been found in certain populations:

Ashkenazi Jewish population (types A and B)
French Canadian population of Nova Scotia (type D)
Maghreb region (Tunisia, Morocco, and Algeria) of North Africa (type B)
Spanish-American population of southern New Mexico and Colorado (type C)

Pick's Disease is sometimes confused with Niemann-Pick but it is a different disease. Additional information can be found on the Pick's Disease support group website.

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