Genetic Testing

Niemann-Pick diseases are acquired through autosomal recessive inheritance, which means that the affected individual inherits two faulty (mutated) genes, one from each parent. If an individual has a single copy of the mutated gene, they are known as a carrier, and it will have no noticeable effect on their everyday lives and health.

The child may inherit identical mutations from each parent (referred to as homozygous), which can sometimes arise through intermarriage, although this may not be obvious over many generations. In other instances the parental mutations may be different and is referred to as heterozygous. 

In every pregnancy of a couple who each carry a copy of the faulty Niemann-Pick gene:

• There is a 25% probability that their child will inherit Niemann-Pick disease (s)
• There is a 25% probability that their child will be unaffected
• There is a 50% probability that their child will be a carrier of the disease

Genetic counselling is a service that provides support, information and advice about genetic conditions. It is conducted by specialist healthcare professionals who have been trained in genetics. Genetic counselling can:

• Provide clear and accurate information about a genetic condition and how it’s inherited
• Provide advice on the likelihood of passing a genetic condition to a child
• Support in understanding the risks, benefits and limitations of genetic testing
• Support in understanding the results of genetic testing and the implications for the family

Genetic counselling is recommended for all couples in which both partners are known to be carriers, or if one partner is a known carrier and the other’s status is uncertain.

Genetic testing (or screening) is a type of medical test that aims to identify changes in chromosomes, genes or proteins. The results of these tests can confirm or rule out a suspected genetic condition (such as Niemann-Pick disease), or help determine a person’s chance of developing or passing on a genetic disorder.

Genetic testing usually involves having a small sample of your blood or tissue taken, as this sample will contain cells which hold your DNA. Your blood can then be tested to find out whether you are carrying a particular mutation, and are consequently at risk of developing a particular genetic condition. More than 1,000 genetic tests are currently used, and more are being developed each year.

Dr. Michael Hughes from UCL explains gene therapy, and explores what this may mean for the NPUK community and broader Niemann-Pick family in this short explainer video.

Prenatal diagnosis for Niemann-Pick disease is possible. If the DNA mutations of both parents are known, then the process of  prenatal diagnosis can be much quicker.

The following tests may be conducted for prenatal diagnosis:

• For all forms of Niemann-Pick disease prenatal diagnosis is available by amniocentesis or CVS (Chorionic Villus Sampling).
• Biochemical testing is available if the pro-band (affected individual) has a classical biochemical phenotype, but not if the pro-band has a variant biochemical phenotype.
• Molecular genetic testing is available if the pro-band has identified mutations in the NPC1 gene.
• Pre-implantation genetic diagnosis (PGD) has been successfully utilised for Niemann-Pick Disease Type B (NP-B) and Niemann-Pick Disease Type C (NP-C). This may be an option for families in which the disease-causing mutations have been identified. Please refer to the Genetic Alliance UK for further information on PGD.

Carrier testing is conducted to determine if a person is a carrier for a specific autosomal recessive disease, such as Niemann-Pick disease. This kind of testing is primarily used by couples who are considering becoming pregnant to determine the risks of their child inheriting a genetic disorder.

Carrier testing is usually only possible once there is an affected person in the family and following the identification of the gene mutation(s). In Niemann-Pick Disease Type C (NP-C), molecular genetic analysis may be used for carrier testing if the specific mutations have been identified in the family. The known mutations of the Niemann-Pick Disease Type A (NP-A) and Niemann-Pick Disease Type B (NP-B) have been well-studied and DNA testing is available; some ethnic groups, including Ashkenazi Jews, North Africans, Arabs and Turks, may have higher frequencies of these conditions.

For the general population, carrier testing for Niemann-Pick disease is not yet available.