How does someone get Gaucher disease?

Gaucher disease is inherited

Much of a person's makeup is a result of what is inherited from each parent. Certain characteristics, such as eye colour, height, and genetic disease are passed from parents to children. The genes for these characteristics are organized on 23 pairs of chromosomes. Genes contain the blueprints that the body's cells use to produce proteins, the building blocks of life. Each chromosome contains thousands of genes. An individual normally inherits one copy of each gene from each parent.

The genes for glucocerebrosidase are also passed on from parents to children. In Gaucher disease, the blueprint for the glucocerebrosidase enzyme (a type of protein), is defective. As a result, the glucocerebrosidase produced from the defective genes is unable to perform its normal function.

 Is the risk of inheriting Gaucher disease the same for males and females?

Copies of the gene for glucocerebrosidase are carried on a chromosome that is not involved in determining an individual's sex. As a result, the defective glucocerebrosidase gene can be passed on to either males or females. One pair of chromosomes, called the sex chromosomes, differs between men and women in a way that determines their sexual identities. The other 22 pairs of chromosomes are called autosomes. The gene for the glucocerebrosidase enzyme is on one of the autosomal chromosome pairs. Gaucher disease is referred to as an autosomal recessive disorder. Recessive refers to the fact that in order to develop the disease, an individual must inherit two defective copies of the gene, one from each parent.

 Who are Gaucher carriers?

A person with one normal gene and one defective gene for glucocerebrosidase is a carrier of Gaucher disease. (Approximately 1 in 10 people in the Ashkenazi population are carriers.) Such individuals will not develop the disease because as long as one of the two genes for glucocerebrosidase is normal, enough glucocerebrosidase can be produced to prevent glucocerebroside from accumulating. Although a Gaucher carrier will have no symptoms of the disease, the odds are 50:50 that the "Gaucher gene" will be passed on to each of his or her children. A child will only develop Gaucher disease if he or she inherits a defective gene from both parents.

 What are the odds of having children that have Gaucher disease or who are Gaucher carriers?

If both parents have normal genes for glucocerebrosidase, each child will inherit two normal genes, one from each parent, and will neither have Gaucher disease nor be a carrier (see below).

If one parent is a carrier of Gaucher disease and the other parent is not, there is a 50:50 chance of having a child who inherits the "Gaucher gene" from the carrier parent, and becomes a carrier of the disease. None of the children will have Gaucher disease, because they will have one normal gene inherited from the other parent (see below).

If both parents are carriers of Gaucher disease, with each pregnancy there is a 25% chance of having a child who inherits one "Gaucher gene" from each parent, and thus has Gaucher disease. There is a 50:50 chance of having a child who inherits a "Gaucher gene" from one parent and a normal gene from the other parent, and becomes a carrier of the disease. Finally, there is a 25% chance for each pregnancy of having a child who inherits two normal genes, one from each parent, and who neither has Gaucher disease, nor is a carrier (see below).

It must be emphasized that the odds for each pregnancy, of inheriting Gaucher disease, are totally independent of whether or not a previous child has the disease. Having one child with Gaucher disease does not mean that the next three children cannot inherit the disease.

 If one parent has Gaucher disease and the other parent neither has the disease, nor is a carrier, all children will inherit the "Gaucher gene" from the parent with the disease, and will become carriers. None of these children will have the disease themselves (see below).

If one parent has Gaucher disease and the other parent is a Gaucher carrier, there is a 50:50 chance of having a child who inherits a "Gaucher gene" from each parent, and thus has the disease. There is also a 50:50 chance of having a child who only inherits the "Gaucher gene" from one parent, and becomes a carrier.

If both parents have Gaucher disease, all of their children will inherit two "Gaucher genes" and will have the disease as well (see below).

Who should be tested for Gaucher disease for carrier status?

Because Gaucher disease is a genetic disorder, all close blood relatives of patients are at risk of having the disease, or are potential carriers of the "Gaucher gene." Families with a history of Gaucher disease may want to discuss the possibility of genetic testing with their physicians. To screen for the disease, a blood sample is taken to measure glucocerebrosidase activity. Depending on the level of activity found, a person may be diagnosed as having Gaucher disease or as a Gaucher carrier. For detecting carriers, the blood test is not always accurate due to the variation in enzyme levels. Amniocentesis and chorionic villi sampling (CVS) can be used to diagnose Gaucher disease early in pregnancy. Genetic counseling is available to couples who are found to be carriers or who have a family history of Gaucher disease.