What is Gaucher disease?
Gaucher disease is a lysosomal storage disorder in which the activity of the enzyme beta-glucocerebrosidase is incredibly low or non-existent. Beta-glucocerebrosidase is responsible for the breakdown of glucocerebroside, a lipid, into the simpler glucose and ceramide molecules. If beta-glucocerebrosidase activity is too low (as in the case of Gaucher disease), then glucocerebroside levels accumulate in cells and cause damage to tissues and organs.
What causes Gaucher disease?
Gaucher disease is an autosomal recessive inherited disorder, which means that a person gets Gaucher disease only if both of their parents were carriers of the disease. Because carriers do not typically show signs or symptoms of Gaucher disease, a person generally does not know they’re a carrier unless they’ve undergone a blood or saliva test.
If a person inherits Gaucher disease, they’ve received a copy of a mutated GBA gene from each parent. The GBA gene is responsible for the production of beta-glucocerebrosidase. When there are defects to the GBA gene, the activity of beta-glucocerebrosidase is significantly reduced, ultimately leading to the buildup of glucocerebroside in cells and the damage of tissues and organs.
How common is Gaucher disease?
It’s estimated that 1 in 60,000 people have Gaucher disease, though the frequency is higher among those of Ashkenazi (Eastern European) Jewish descent. Among that population, approximately 1 in 450 people has Gaucher disease while 1 in 10 may be carriers of the disease.
How is Gaucher disease diagnosed?
Gaucher disease can be diagnosed with an enzyme assay (by way of a blood test) or with genetic analysis. Blood tests are used to check levels of glucocerebrosidase (the enzyme associated with Gaucher disease) in leukocytes (white blood cells), fibroblasts (cells that help make connective tissues), or urine. In those with Gaucher disease, the level of glucocerebrosidase will be incredibly low. Enzyme assays, however, can not specify the type of Gaucher disease a person has nor the severity of the disease.
Genetic analysis can be used to look for mutations associated with Gaucher disease. The four common mutations of the gene responsible for glucocerebrosidase production are N370S, L444P, 84gg, and IVS2[+1]. Enzyme assays in combination with genetic analysis can help specialists pinpoint the subtype of Gaucher disease.
What are the symptoms of Gaucher disease?
There are multiple types of Gaucher disease, and each type may present its own symptoms.
In Gaucher disease Type I, symptoms can range from mild to severe and typically include enlarged liver and/or spleen, anemia (or a low level of red blood cells), easy bruising as a result of decreased blood platelets, and various bone problems including pain, fracturing, and arthritis. Lung disease may also be present.
Gaucher disease Type II and Type III affect the central nervous system. In addition to the symptoms of Type I, Types II and III present unusual eye movement, seizures, and brain damage. Gaucher disease Type II is a life-threatening condition and many diagnosed with this type don’t survive infancy. While Type III is also life-threatening, symptoms typically progress at a slower rate than Type II.
In addition to Types I, II, and III, Gaucher disease also has a perinatal lethal form, which causes severe complications even before birth, and a cardiovascular form which involves calcification of the heart valves. The perinatal lethal form of Gaucher disease may present skin abnormalities (including dry or scaly skin), excessive swelling, and serious neurological problems.
Although some symptoms (such as enlarged liver/spleen and anemia) tend to be common across types, it’s important to remember that symptoms can vary even between individuals with the same type of Gaucher disease.
What are the treatment options for Gaucher disease?
Currently, no treatments exist for Gaucher disease Type II.
For those with Gaucher disease Type I or III, treatments are available in the form of enzyme replacement therapy or an oral medication. Enzyme replacement therapies include Cerezyme (imiglucerase for injection), Elelyso (taliglucerase alfa), and VPRIV (velaglucerase alfa for injection). Oral medications include Cerdelga (eliglustat) and Zavesca (miglustat).