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.

Type C Niemann-Pick usually affects children of school age, but the disease may strike at any time from early infancy to adulthood. Symptoms may include:

• Jaundice at (or shortly after) birth
• An enlarged spleen and/or liver
• Difficulty with upward and downward eye movements (Vertical Supranuclear Gaze Palsy)
• Unsteadiness of gait, clumsiness, problems in walking (ataxia)
• Difficulty in posturing of limbs (dystonia)
• Slurred, irregular speech (dysarthria)
• Learning difficulties and progressive intellectual decline (dementia)
• Sudden loss of muscle tone which may lead to falls (cataplexy)
• Tremors accompanying movement and, in some cases, seizures

Symptoms of all forms of Niemann-Pick are variable -- no single symptom should be used to include or exclude Niemann-Pick as a diagnosis. A person in the early stages of the disease may exhibit only a few of the symptoms. Even in the later stages of the disease, not all symptoms may be present.

In addition, symptoms are progressive but the rate of progression is different from person to person. Finally, the symptoms of Niemann-Pick are also found in other, more common, diseases. These factors make it difficult to diagnose Niemann-Pick without appropriate testing.

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. This test can identify those with the disease, but not those who may be carriers.

It is, however, 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 a 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 two genes that cause Niemann-Pick type C disease.

Additional tests might include:

• Slit-lamp eye exam
• Liver biopsy or bone marrow aspiration looking for foamy histiocytes that have a mulberry appearance (a particular type of cell with a characteristic appearance)
• Liver biopsy (usually not necessary)
• Sphingomyelinase assays