Medical Genetics and Genomics

Gaucher Disease

Gaucher disease is caused by mutations in the GBA gene. Mutations in the GBA gene result in reduced activity of an enzyme in the body called acid beta-glucosidase that is necessary to break down a fatty substance called glucocerebroside, so the body can recycle it. In Gaucher disease, this fatty material collects in the tissues of the body. As time goes by, this storage can damage tissues and organs and causes the typical features of Gaucher disease.

Who is Affected

Type I Gaucher disease is the most common genetic disorder in Jewish individuals of Central and Eastern European ancestry (Ashkenazi Jews). Everyone has two copies of the GBA gene, one passed on from mom and one passed on from dad. To have Gaucher disease, both copies of the gene must have mutations that cause it to not work properly. This is called autosomal recessive inheritance. Approximately one in fifteen Ashkenazi Jews carry a mutation in one copy of the GBA gene, which means they do not have symptoms themselves but their children are at risk of having the disease. Although Gaucher disease is more common in the Ashkenazi Jewish population, people who have Gaucher disease can be of all ethnic groups.

Types of Gaucher Disease

Several types of Gaucher disease have been described based on their signs and symptoms, but there is a wide variability in the severity of disease even within the same subtype. The most common form, type 1 Gaucher disease, ranges from mild to severe disease, which can begin any time from childhood to adulthood. Over time, people with Gaucher disease may develop an enlarged liver and/or spleen, low bone density or bone/joint pain, and blood problems including a tendency to bleed and anemia. Children may have delayed vertical growth. The brain and spinal cord (central nervous system) are not typically affected in type 1 Gaucher, but can be involved in type 2 and type 3 Gaucher.  

Patients with type 2 Gaucher disease have severe, progressive brain involvement that can include abnormal eye movement and brain damage, in addition to the liver, spleen, and bone symptoms in type 1. Patients with type 2 disease usually have symptoms very early in life and usually pass away before age 2. Patients with type 3 Gaucher disease also have involvement of the brain, but it is generally less severe, and may progress slower than type 2.

Gaucher Disease Treatment

There are two FDA-approved treatments for type 1 Gaucher disease. Many patients with type 1 Gaucher disease receive enzyme replacement therapy (ERT), which replaces the missing beta-glucosidase enzyme. ERT can decrease the size of the liver and spleen, stabilize or reverse bone disease, and improve blood counts. It is given intravenously (IV) every two weeks for life.  The second method of treatment for Gaucher disease is based on the principle of reducing the fatty substance, glucocerebroside, that accumulates to form Gaucher cells. This is called substrate reduction therapy (SRT). This is an oral medication that may be considered in a subset of adults with Gaucher disease. SRT is not yet approved for children.