Niemann-Pick disease refers to a group of diseases passed down through families (inherited) in which fatty substances called lipids collect in the cells of the spleen, liver, and brain.

There are four most commonly recognized forms of the disease: Types A, B, C, and D. Types A and B are also called Type I. Types C and D are also known as Type II.

Each type involves different organs and may or may not involve the central nervous system or respiratory system. Each one can cause different symptoms and may occur at different times throughout life, from infancy to adulthood.

Niemann-Pick disease Type A and B occur when cells in the body lack an enzyme called acid sphingomyelinase (ASM). ASM helps break down (metabolize) a fatty substance called sphingomyelin, which is found in every cell of the body. If ASM is missing or does not work properly, sphingomyelin builds up inside cells. This leads to cell death and makes it hard for organs to work properly. Type A occurs in all races and ethnicities, but higher rates are seen in the Ashkenazi (Eastern European) Jew population.

Niemann-Pick Type C occurs when the body can not properly break down cholesterol and other lipids (fats). This leads to too much cholesterol in the liver and spleen and excessive amounts of other lipids in the brain. There may be reduced ASM activity in some cells. Type C Niemann-Pick disease has been reported in all ethnic groups but it is most common among Puerto Ricans of Spanish descent.

Type D Niemann-Pick involves a defect that interferes with the movement of cholesterol between brain cells. It is now thought to be a variant of type C. This type of Niemann-Pick disease has only been found in the French Canadian population of Yarmouth County, Nova Scotia.

An adult-onset form of Niemann-Pick disease has been suggested. It is sometimes referred to as Type E disease.

Type A usually begins in the first few months of life. Symptoms may include:

• Abdominal (belly area) swelling within 3 - 6 months
• Cherry red spot in the eye
• Feeding difficulties
• Loss of early motor skills (gets worse over time)

Type B symptoms are usually milder and occur in late childhood or adolescence. Abdominal swelling may be seen in early childhood, but there is almost no neurological involvement, such as loss of motor skills. Some patients may have repeated respiratory infections.

Type C usually affects school-aged children, but the disease may occur any time between early infancy to adulthood. Symptoms may include:

• Difficulty in posturing of limbs (dystonia)
• Enlarged spleen
• Enlarged liver
• Jaundice at (or shortly after) birth
• Learning difficulties and progressive intellectual decline (dementia)
• Seizures
• Slurred, irregular speech
• Sudden loss of muscle tone which may lead to falls (cataplexy)
• Tremors
• Trouble moving the eyes up and down (vertical supranuclear gaze palsy)
• Unsteady gait, clumsiness, walking problems (ataxia)

Symptoms of Type D are similar to Type C.

Type E occurs in adults. Symptoms include swelling of the spleen and neurological problems. Little is known about this rare type of Niemann-Pick disease.

Symptoms and disease progression of all forms of Niemann-Pick vary from person to person. No single symptom should be used to include or exclude Niemann-Pick as a diagnosis. Other, more common, diseases may cause symptoms similar to Niemann-Pick.

A person in the early stages of the disease may show only a few symptoms. Not every symptom will be seen in the later stages of the disease.

Type A and B are diagnosed by measuring the amount of ASM in white blood cells. The test can be done using a blood or bone marrow sample. Such testing can tell who has the disease, but does not reveal who may be carriers. DNA tests can be done to diagnose carriers of Type A and B.

A skin biopsy is usually used to diagnose Type C and Type D Niemann-Pick. Laboratory scientists will watch how the skin cells grow and study how they move and store cholesterol. DNA tests may also be done to look for the two genes that cause Niemann-Pick disease Type C.

Additional tests might include:

• Slit-lamp eye exam
• Liver biopsy or bone marrow aspiration
• Liver biopsy (usually not necessary)
• Sphingomyelinase assays