Niemann-Pick

Alternative names

Sphingomyelinase deficiency (type A Niemann-Pick disease)

Definition

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.

Causes, incidence, and risk factors

All forms of Niemann-Pick are genetic diseases inherited in an autosomal recessive manner.

Types A and B Niemann-Pick are both caused by deficiency of a specific enzyme, acid sphingomyelinase (ASM). If ASM is absent or not functioning properly, sphingomyelin cannot be broken down (metabolized) properly and accumulates within the cells, eventually causing cell death and the malfunction of major organ systems.

Type C Niemann-Pick is very different. Patients with type C are not able to break down cholesterol and other lipids (fats) properly. Consequently, excessive amounts of cholesterol accumulate in the liver and spleen and excessive amounts of other lipids accumulate in the brain. This defect in metabolism occasionally leads to reduced ASM activity in some cells.

Type C Niemann-Pick disease has been reported in all ethnic groups but it is most prevalent among 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 people with type D. 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.

Symptoms

Type A Niemann-Pick begins in the first few months of life. Symptoms may include:

• Feeding difficulties
  
• A large abdomen within 3 to 6 months
  
• Progressive loss of early motor skills
  
• Cherry red spot in the eye
  

Type B is biochemically similar to type A, but the symptoms are more variable. Abdominal enlargement may be detected in early childhood, but there is almost no neurological involvement, such as loss of motor skills. Some patients may develop repeated respiratory infections.