Medical Genetics and Genomics

Niemann-Pick Disease

Niemann-Pick Disease (NPD) refers to a group of autosomal recessive inherited diseases, meaning that the mother and father must both pass one nonworking copy of the gene to the child in order for the child to develop the disease. The three most commonly recognized forms are called Types A, B, and C. Types A and B NPD are both caused by the reduced activity of an enzyme called acid sphingomyelinase (ASM). The function of ASM is to break down a fatty substance called sphingomyelin. When ASM is not working properly, sphingomyelin builds up within the tissues of the body and leads to the symptoms associated with NPD.

NPD type A appears during infancy and is described by an enlarged liver and spleen, failure to gain weight and grow at the expected rate (failure to thrive), and gradual deterioration of the nervous system. NPD-A is also known as the neurological type, due to the involvement of the nervous system. Children affected by this condition generally do not survive past early childhood.  There is no treatment for NPD-A.

NPD Type B is very variable and has a range of symptoms that may include enlargement of the liver and spleen, growth delays, and problems with lung function including frequent lung infections. Other signs include blood abnormalities such as elevated levels of cholesterol and other lipids (fats), and decreased numbers of blood cells involved in clotting (platelets). Most patients with NP-B develop symptoms when they are children, although some have milder disease and are not diagnosed until they are adults. NP-B is known as the non-neurological type because the brain is not usually affected. The life expectancy of Type B NPD patients is highly variable depending on the severity of their symptoms.

Type C NPD, although similar in name, is very different in that patients with Type C NPD are not able to metabolize cholesterol properly. As a result, large amounts of cholesterol accumulate within the liver, spleen, and brain. In young children, many of the symptoms of the three NPD types appear similar. We now know that Types A and B NPD are two forms of the same disease caused by changes in the ASM gene, while Types C and D NPD are two forms of a distinct disease caused by abnormalities in a different genes related to how the body breaks down cholesterol.

Niemann-Pick Disease (Types A&B) Treatment

There is no specific treatment or approved medical therapy for NP-B. However, clinical trials are currently in process to evaluate if a new investigational drug for NP-B. This is a treatment based on the principle of replacing the enzyme, acid sphingomyelinase that is missing or not working properly in people with Niemann-Pick disease called Enzyme Replacement Therapy (ERT). It is being studied for the treatment of non-neurological symptoms of Niemann-Pick type B and has been granted Breakthrough Therapy designation by the FDA to expedite the development and review process.