Gaucher’s Disease: an Inborn Error of Metabolism

Gaucher disease was first recognized by the French doctor Philippe Gaucher, who originally described it in 1882 and lent his name to the condition.

It is an autosomal recessive genetic disorder caused by a lack of the enzyme glucocerebrosidase (“NINDS”). When this enzyme is not present, there is an accumulation of lipids in cells and certain organs. This accumulation can lead to further problems such as enlargement of the spleen and liver, painful bone lesions, swelling of lymph nodes, and anemia to name a few. This disorder is most common in the Ashkenazi Jewish population, but can occur in any race (“NINDS”).

The genetics of Gaucher disease as well as the symptoms, treatments, and testing will be further discussed in the remainder of this paper. Background Gaucher disease is the most common lysosome storage disorder (LSD). As discussed above, people with Gaucher disease lack the normal form of the glucocerebrosidase enzyme and are unable to break down glucocerebroside in the lysosomes. Also in the lysosomes are macrophages that eat worn-out cells and recycle them.

Without the glucocerebrosidase enzyme, glucocerebroside builds up in the lysosomes and prevents macrophages from functioning properly.Figure 1 in the appendix shows a Gaucher cell in which the nucleus is pushed off to the side, and the remainder of the cell is filled with abnormal lipids. Genetics There are three types of Gaucher disease that are inherited in an autosomal recessive fashion. Both parents must be carriers in order for a child to be infected.

If two carriers have children there 25% chance that each child born to them will have the disease. Figure 2 in the appendix shows the expected progeny for two parents who are carriers for Gaucher disease.There are three types of Gaucher disease. In general, the later in life the first symptoms appear, the less likely that the disease will be severe.

Type I Type I is by far the most common form of Gaucher disease. The symptoms of Type I can occur at any age and include an enlarged spleen and liver, bone disease, and anemia. Many people with Type 1 disease have no clinical symptoms and lead normal lives. In some cases, however, the disease may become life-threatening.

(“NINDS”) Figure 3 shows a young Ashkenazi boy with Type I Gaucher disease.Type II is characterized by severe neurological involvement in the first year of life, and is the rarest type of Gaucher disease. This type is also known as infantile Gaucher disease due to the apparent symptoms in the first few months of life. These include an enlarged spleen and liver and extensive brain damage. A child with Type II usually dies by two years of age. (“Living with Guacher Disease”) Type III Type III is characterized by a slowly progressive neurological disease and is also very rare.

Symptoms become apparent in early childhood, and most victims will live into their thirties.The symptoms are the same as Type I, except that there is brain damage in Type III. (“NINDS”) Diagnosis The disease is not hard to test for; however, its symptoms can be easily confused and mistaken for other diseases. For example, if a patient has low platelet counts, the physician may first test for leukemia.

Or if a patient complains about joint pain, the physician may first suspect arthritis. Gaucher disease may however be suspected in a patient who has an enlarged spleen or a tendency toward bleeding. Gaucher disease is most apparent in laboratory analysis.These symptoms include elevated levels of acid phosphatase and skeletal abnormalities revealed by X-rays.

(“Living with Gaucher Disease”) If Gaucher disease is already strongly suspected from the start, then the diagnosis can be established by a blood test showing a significantly decreased activity level of glucocerebrosidase in white blood cells. Treatment For Type I and most Type III patients, enzyme replacement treatment (more specifically known as Cerezyme therapy) with intravenous recombinant glucocerebrosidase can dramatically decrease liver and spleen size and reduce skeletal abnormalities.Cerezyme acts like the naturally occurring enzyme glucocerebrosidase to break down the fat molecules that have accumulated in Gaucher cells (“Treatment”). Bone marrow transplantation (a procedure to replace damaged or destroyed blood-forming cells) can reverse the non-neurological effects of Type I Gaucher disease, but it carries a high mortality rate due to imperfect donor matches (Kashiro). In the case of a severe and persistent lowering of the blood count, physicians may decide to remove all or part of the spleen.

However, removal of the spleen leads to an increased risk of bacterial diseases, so it is usually delayed for as long as possible. There is no effective treatment for severe brain damage that may occur in patients with Types II and III Gaucher disease. Prevention Genetic counseling is recommended for prospective parents with a family history of Gaucher disease. Testing can determine if parents carry the gene that could pass on Gaucher disease to their offspring. A prenatal test can also tell if the fetus has Gaucher syndrome.