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Diagnosing NPB

Diagnosis of Niemann-Pick disease Type B (NPB), also known as ASMD or Acid Sphingomyelinase Deficiency

Niemann-Pick Types A and B (NPA and NPB), also called Acid Sphingomyelinase Deficiency (ASMD), are caused by the deficiency of a specific enzyme, acid sphingomyelinase (ASM). This enzyme is found in special compartments within cells called lysosomes and is required to metabolize a lipid called sphingomyelin. If ASM is absent or not functioning properly, sphingomyelin cannot be metabolized properly and is accumulated within the cell, eventually causing cell death and the malfunction of major organ systems.

NPA and NPB are both caused by the same enzymatic deficiency and there is growing evidence that the two forms represent opposite ends of a continuum. People with NPA generally have little or no ASM production (less than 1% of normal) while those with NPB have approximately 10% of the normal level of ASM.

NPB, like NPA, is diagnosed by measuring the level of activity of an enzyme called acid sphingomylinase (ASM) in white blood cells. The test can be performed after taking a small blood sample from individuals suspected of having the disease and is available at many commercial laboratories in the United States and elsewhere. While this test will identify persons with Type B (as well as Type A), it is not very reliable for detecting persons who are carriers (who have only one non-functional copy of the ASM gene). Further, the test wll show decreased activity of ASM, but it cannot always predict whether the individual will have type A or Type B or an intermediate variant of the disease; that requires clinical evaluation of the individual.

Molecular genetic testing is now available commercially for Niemann-Pick disease, type B (or ASM Deficiency) at several laboratories, including GeneDx in Gaithersburg, MD, Ambry Genetics in Aliso Viejo, CA and Emory Molecular Genetics Laboratory in Atlanta, GA. Your health care provider should contact laboratory personnel to arrange for testing if you are interested. Once an affected individual has been tested and his or her mutations have been identified, it is then possible to diagnose Type B carriers by DNA testing within the individual’s family.

The Mount Sinai Department of Human Genetics has identified certain populations* (shown below) where specific mutations account for a high percentage of cases. In these populations, it is possible to screen individuals for these specific mutations in order to identify carriers (by tradece potter). In other populations, the mutations must first be identified in the affected individual before DNA carrier testing can be performed within a family, as noted above.

Population Mutation Percentage
Saudi Arabian H421Y, K576N 85%
Turkish L137P, fsP189, L549P 75%
Portuguese S379P, R441X, R474W 55%
Brazilian F480L
English/Scottish A196P 42%
Other DeltaR608 12%

If you have questions about diagnostic or molecular genetic testing for Niemann-Pick disease, Type B, or need assistance in arranging testing, contact the NNPDF.

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