Niemann-Pick Disease, Type A

Niemann Pick disease (NPD) is an inherited disorder that is due to defects in an enzyme called acid sphingomyelinase. This condition leads to abnormal accumulation of lipids in spleen, liver, lungs, bone marrow, and brain. NPD type A is known as the neurological type, which appears during infancy, with intellectual disability and death in early childhood. A less severe type of the disease, NPD type B is known as the non-neurological type because the neurological system is usually not affected. Children with this condition usually survive into adulthood. At this time, there is no effective treatment for NPD type A. Pathogenic variants in the gene SMPD1 can cause either type A or type B of NPD.

Niemann Pick disease is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for Niemann Pick disease. However, there is an increased risk to have children affected with Niemann Pick disease. Testing of reproductive partners is recommended for carriers of Niemann Pick disease.

In the general population, about 1 in 250,000 individuals are affected with Niemann Pick disease type A or B. Niemann Pick disease type A is more frequently observed in the Ashkenazi Jewish population, occuring in about 1 in 40,000 newborns. Niemann Pick disease type B has been reported in various different ethnicities.

Genetic Home Reference: Niemann Pick Disease (http://ghr.nlm.nih.gov/)

OMIM: [Niemann Pick Disease, Type A: 257200] (http://www.ncbi.nlm.nih.gov/omim)
GeneReviews: Acid Sphingomyelinase Deficiency (http://www.ncbi.nlm.nih.gov/books/NBK1370/)

• Full gene sequencing