FAQ

Gaucher disease is an inherited condition caused by abnormal functioning of a gene located on chromosome #1. Normally, this gene produces an enzyme called glucocerebrosidase which functions inside cells, in the lysosome. Glucocerebrosidase breaks down and recycles a fat called glucocerebroside, which is a normal part of the cell membrane. In people with Gaucher disease, the body does not produce enough enzyme, and glucocerebrosides cannot be broken down and recycled. This fat then accumulates in the liver, spleen and bone marrow, causing them to lose their normal functions.

How Does Gaucher Disease Present?

There are three forms of Gaucher disease. Type I is the most common form of the disease and does not affect the central nervous system (non-neuronopathic). The signs and symptoms of this form of the disease vary greatly from one person to another. The most common symptom is an enlarged spleen, which is generally painless. Other symptoms may include an enlarged liver, frequent nosebleeds, bruising, bone pain, and a lack of energy. Some people may experience only a few of these symptoms, while others have many. One person may have bone problems while another may have only an enlarged spleen. Symptoms can be present in any combination. In addition, children with Type I Gaucher disease may be shorter than their peers and have delayed puberty.

Type II is much less common and more severe than Type I. Symptoms usually appear in an infant several months after birth. The disease affects the infant's nervous system, which can result in an inability to support the head and difficulty breathing. Infants with this type of the disease usually die by the time they are two years old.

Type III is also less common than Type I. Symptoms appear between infancy and the early teen years. This form of the disease also affects the person's central nervous system. As a result, affected individuals may experience irregular eye movements, seizures and mental retardation. Type III disease is most prevalent in a specific isolate in Sweden (Norrbottnia) but also occurs in the general population.

Who Is At Risk For Gaucher Disease?

Gaucher disease may occur among every nationality and ethnic group, but it is most common among individuals of Jewish descent of Eastern or Central Europe (Ashkenazi Jews). Type I Gaucher disease, in fact, is the most common genetic disease among people of a Jewish descent. An estimated one in 10 Ashkenazi Jews is a carrier of Gaucher disease. Types II and III, however, are not more prevalent among the Jewish population.

How Is Gaucher Disease Inherited?

Gaucher disease is transmitted in a pattern called autosomal recessive inheritance. In other words, each of us has 2 genes which provide instructions for making the enzyme in question. In most individuals, both genes work properly.

If 1 of the 2 genes is nonfunctional, a person is said to be a carrier. carriers are healthy and have no symptoms of gaucher disease because only one functional gene is needed to produce sufficient amounts of the enzyme to carry out normal body functions. If both genes are nonfunctional, an individual has Gaucher disease.

• If both parents are carriers, there is a 1 in 4 (25%) chance in each pregnancy of having a child with Gaucher disease. The same parents have a 1 in 2 (50%) chance of having a child who is a carrier.
• If 1 parent is a carrier and 1 is not, there is a 50% chance with each pregnancy that the child will be a carrier.
• If 1 parent has Gaucher disease and the other does not and is not a carrier, all of their children will be carriers.
• If 1 parent has Gaucher disease and the other is a carrier, there is a 50% chance that each child will have Gaucher disease and a 100% chance that the child will be a carrier.

How Is Gaucher Disease Diagnosed?

A blood test is used to determine whether a person has Gaucher disease. This blood test is also used to identify people who may be carriers of Gaucher disease but do not have symptoms. The blood test involves two parts: enzyme (glucocerebrosidase) activity level and DNA analysis of the gene for glucocerebrosidase.

The first test involves measuring the level of glucocerebrosidase enzyme activity. Individuals who are affected with Guacher disease will have very low levels of enzyme activity. Carriers have enzyme activity levels that are intermediate between those with Gaucher disease (with 2 nonfunctional genes) and non-carriers (with 2 functional genes). This form of testing has an accuracy rate of about 90%.

A second type of carrier testing involves looking at the genetic changes (mutations) which make the genes nonfunctional. In the Ashkenazi Jewish population, 4 common mutations (N370S, L444P, 84GG, and IVS2) account for approximately 95% of all nonfunctional Gaucher genes. If a mutation is identified, the individual is a definite carrier. If an individual tests negative for these 4 mutations, there is still a chance that the person is a carrier but was missed because other mutations have not yet been identified. A smaller percentage of non-Jewish individuals carry one of these common mutations.

Is There An Effective Treatment For Gaucher Disease?

Yes, a few years ago, enzyme replacement therapy became available as the first effective treatment for Gaucher disease.The treatment consists of a modified form of the glucocerebrosidase enzyme which is given intravenously over one to two hours, usually every two weeks. Enzyme replacement therapy can stop progression and often reverse the symptoms of Gaucher disease.

New oral therapy is available in Europe. Clinical trials are being conducted in the United States.

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