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Diagnosis of Niemann-Pick Type C

Niemann-Pick Type C (NPC) is a rare and extremely variable condition and therefore may not be recognized by some health care providers. For those specialists who do suspect this diagnosis in a patient, it can be determined by taking a small piece of skin ("skin biopsy"), growing the cells ("fibroblasts") in the laboratory, and studying their ability to transport and store cholesterol.

The transport of cholesterol in the cells is studied by measuring conversion of the cholesterol from one form to another ("esterification"). The storage of cholesterol is assessed by staining the cells with a chemical ("filipin") that glows under ultraviolet light. This can show whether the cholesterol is being stored inappropriately in lysosomes, the recycling centers of the cell. It is important that both the transport and storage tests be performed, since reliance on one or the other may lead to an incorrect diagnosis or a missed diagnosis of a variant form of NPC.

If a clinician suspects NPC in a patient, there are only 2 laboratories in the United States that do this diagnostic testing: 1) the Mayo Clinic Biochemical Genetics Laboratory in Rochester, MN and 2) the Lysosomal Disease Testing Laboratory at Thomas Jefferson University in Philadelphia, PA. It is important that the health care provider who is caring for your child contact the laboratory because laboratory personnel are not permitted to discuss testing directly with patients or their families. The health care provider will be given directions for collecting the sample and sending it to the laboratory so that it can be properly analyzed.

In 1997, the NPC1 gene was identified. Mutations, or disease-causing changes, in this gene are responsible for about 95% of all NPC cases. Since 1997, over 250 different genetic mutations related to NPC have been identified in this gene and in the second NPC gene, called NPC2. Overall, in about 95% of cases, it is possible to identify the genetic changes that have caused the disease if the diagnosis of NPC has first been confirmed by the testing outlined above. However, because there are so many unique mutations in these genes, and there are patients with classic NPC in whom mutations have not been identified, it is not optimal to use genetic testing as a general diagnostic tool. In addition, genetic testing can be performed to identify carriers in families where the mutation is known. More recently, it has also been used to help better define the carrier risk for partners of known carriers.

There are now three laboratories in the United States that perform genetic testing for NPC: 1) GeneDx in Gaithersburg, MD, 2) Emory Molecular Genetics Laboratory, and 3) Mayo Clinic Molecular Genetics Laboratory. As with the diagnostic testing laboratories, the health care provider who is caring for your child should contact the laboratory for testing details.

For additional information about options for genetic testing, contact the NNPDF.

[June 30, 2010 mem]