How is NPD Diagnosed?
Type A and B Niemann-Pick are diagnosed by measuring the ASM (acid sphingomylinase) activity in white blood cells. The test can be performed after taking a small blood sample from suspected individuals. While this test will identify persons with Type A and B (two mutated genes), it is not very reliable for detecting persons who are carriers (only one mutated gene).
It is 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. The Mount Sinai Department of Human Genetics has identified certain populations (shown below) where specific mutations account for a high percentage of cases. In other populations, the mutations must first be identified for the individual before DNA carrier testing can be performed.
| Population | Mutations | Percentage | NP Type |
| Ashkenazi Jewish | R496L, L302P | 53% | A |
| Saudi Arabian | H421Y, K576N | 85% | B |
| Turkish | L137P, fsP189, L549P | 75% | B |
| Portuguese / Brazilian | S379P, R441X, R474W, F480L | 55% | B |
| English / Scottish | A196P | 42% | B |
| Other | DeltaR608 | 12% | B |
| Type B statistics are from "The Demographics and Distribution of Type B Niemann-Pick Disease: Novel Mutations Lead to New Genotype/Phenotype Correlations" by Simonaro CM, Desnick RJ, McGovern MM, Wasserstein MP, Schuchman EH in the American Journal of Human Genetics, Oct 4, 2002. | |||
| Type A statistics are from "Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients" by Levran O, Desnick RJ, Schuchman EH in Blood, Oct 15, 1992. | |||
Type C Niemann-Pick is initially diagnosed by taking a small piece of skin ("skin biopsy"), growing the cells ("fibroblasts") in the laboratory, and then 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 compound ("filipin") which glows under ultraviolet light. It is important that both the transport and storage tests be performed, since reliance on one or the other may lead to the diagnosis being missed in some cases.
Since 1997, over 120 genetic mutations related to Type C have been identified. The number of unique mutations precludes use of genetic testing as a general diagnostic tool. However, genetic testing can be performed to identify carriers in families where the mutation is known. The Mayo Clinic has done extensive DNA testing and counseling for patients and families with NP Type C. For additional information about options for genetic testing, contact Cate Walsh Vockley, the National Niemann-Pick Disease Coordinator.
Because Niemann-Pick Type C is rare and its symptoms are quite variable, it is not widely known even in the medical community. While education efforts by NNPDF have increased awareness of the disease, there are still instances of misdiagnosis and/or delayed diagnosis. If your child is exhibiting symptoms of Niemann-Pick, you may need to ask your doctor to consider the possibility of NP.