• Overview
• Inheritance
• Symptoms
  • Liver and Spleen
  • Lungs
• Testing
• Treatment
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Testing

Diagnosis

Enzyme Testing
The most accurate diagnosis of both types A and B NPD is made based on the results of a blood test that measures the level of ASM enzyme activity. In people with NPD, the amount of enzyme activity is much lower than normal. People with type A NPD generally have less than 5% of the normal ASM level, and people with type B NPD generally have about 5-10% of the normal ASM level. Enzyme testing is not reliable for detecting NPD carriers, since the range of ASM levels in carriers and non-carriers overlaps.

Enzyme testing is not done to diagnose type C NPD. Instead, the diagnosis is made with two types of cholesterol tests (esterification studies and filipin staining). These tests are performed on skin cells (fibroblasts) taken by biopsy.

Bone marrow biopsy
A diagnosis of NPD may also be made based on the results of a bone marrow biopsy, which is sometimes done to determine the cause of hepatosplenomegaly (enlarged liver and spleen). The presence of NPD cells in the bone marrow indicates that a person has NPD but does NOT indicate which type of NPD. Further testing is needed to determine NPD type. If type A or B NPD is already suspected, enzyme testing is usually performed first, since this testing is easier, provides more complete information (including NPD type), and is less invasive for patients. If enzyme testing indicates NPD, then a bone marrow biopsy does not need to be done.

DNA testing
DNA testing, also done on the blood, may detect gene mutations that cause types A and B NPD. (DNA testing is not currently available for type C NPD.) While 95% of type A NPD is generally caused by the same five mutations, less is known about the mutations that cause type B NPD. Many of the mutations in type B NPD are likely to be unique to a particular family.

DNA testing is not generally done to diagnose type B NPD; however, it may be useful to confirm a diagnosis made by enzyme testing. DNA test results may also give more information about a person's NPD; for example, people with NPD who have at least one copy of the deltaR608 mutation have type B NPD. However, DNA test results do not necessarily relate to the severity of the disease or to a person's specific symptoms, and the test result will not change medical treatment. Identifying which NPD gene mutations are present in an affected person may also be helpful to other family members who wish to know if they are a carrier of one of those mutations. Carrier testing is available to relatives of people with NPD.

Carrier testing by DNA analysis is also available for partners of NPD carriers and partners of people with type B NPD, so that couples may learn if their children are at risk to inherit the disease.

Prenatal diagnosis of NPD may be available in pregnancies involving a fetus known to be at risk.

DNA testing for NPD is performed only in some specialized genetics laboratories. Generally, people who have DNA testing first meet with a genetic counselor, who can explain the testing in more detail and answer any questions. The genetic counselor can also help explain the test results, once they are available. Cindy Johnston, MS is a genetic counselor at the Center; she is available to meet with patients to discuss DNA testing and other genetic issues.