Carrier detection in Niemann-Pick type C disease

As Niemann-Pick type C disease (NP-C) is an autosomal, recessive condition, for each pregnancy there is a 25% chance that the offspring of a NP-C carrier couple will receive both mutated NP-C genes and inherit the disease, a 50% chance that the offspring will be a carrier, and a 25% chance the offspring will neither inherit NP-C nor be a carrier.¹

NP-C carriers can be identified via molecular analysis of NPC1 or NPC2 genes if it has been confirmed that a family has a NPC1 or NPC2 mutation.² Biochemical testing is not appropriate as it cannot reliably differentiate between carriers and non-carriers.²

Pregnant women with a 25% risk of NP-C in their unborn child should be offered prenatal testing. This can be achieved by either biochemical (only if the ‘classic' phenotype has been established in the proband) or genetic (only if NPC1 or NPC2 mutations have been identified in the proband) testing of fetal cells obtained via amniocentesis at 15-18 weeks or chorionic villus sampling at 10-12 weeks.¹

Genetic counseling should be offered to individuals and families affected by NP-C, including those who are carriers, or at risk of being carriers.^1,2 Providing information on the genetic risks (i.e. the best time to determine genetic risk, clarification of carrier status, prenatal testing etc.) will enable individuals to make informed decisions, particularly regarding family planning.¹

References

1. Wraith JE, Imrie J. Understanding Niemann-Pick disease type C and its potential treatment. UK Blackwell Publishing, 2007.
2. Patterson MC. Niemann-Pick disease Type C. Gene Reviews 2007a (updated 9 July). Accessible at: www.geneclinics.org. Accessed October 2008.