Niemann-Pick Disease (SMPD1-Related) (SMPD1)

Niemann-Pick disease (SMPD1-related) is an autosomal recessive neurodegenerative disorder caused by pathogenic variants in the gene SMPD1. While it has been reported in patients of various ethnicities, it is more common in individuals of Ashkenazi Jewish descent due to the presence of a founder mutation. Two different phenotypes have been associated with pathogenic variants in this gene, known as Niemann-Pick disease, types A and B. Type A, which is the most severe, manifests in infancy with an enlarged liver and spleen and failure to thrive resulting from feeding difficulties. Patients develop hypotonia and severe developmental delay and intellectual ability. As the brain disease progresses, patients develop spasticity and rigidity of limbs. Death usually occurs at ages 2 to 3. Type B does not involve major neurological manifestations, unlike type A. Features include frequent respiratory infections and breathing difficulties, as well as enlarged organs including the liver, spleen and kidney. A subset of patients may have intellectual disability or psychiatric disorders. Onset is in infancy or childhood, but many patients survive into adulthood. Several specific variants have been associated with either type A or type B. The pathogenic variant that is commonly found in the Ashkenazi Jewish population usually results in type A disease.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):