Gaucher disease is a rare genetic disorder that results in accumulation of fatty molecules called cerebrosides. It can have serious effects on numerous body organs including the liver, spleen, bones, and central nervous system. Treatments based on molecular biology are becoming available, but are very expensive.
Gaucher disease was first described by the French physician Philippe Gaucher in 1882. Gaucher disease is the most common of a class of diseases called lysosomal storage diseases, each of which is characterized by the accumulation of a different chemical substance. Gaucher disease is characterized by a wide array of different symptoms and the severity of the disease ranges from undetectable to lethal.
Three forms of the disease are recognized: types I, II, and III. Type I is by far the most common and shows the mildest symptoms. It is non-neuronopathic, meaning that the nervous system is not attacked. The onset of type I can occur at any age in childhood or adult life. Type II, the infantile form, is neuronopathic; nervous system effects are severe, and victims often die within the first year of life. Type III most often has its onset during childhood and has some of the features of both the adult and infantile forms.
The three forms also differ in that type I is most common in persons of eastern European Jewish descent. Among this population, the disease occurs ar a rate of 1 in 450 live births, making it the most common genetic disease affecting Jewish people. The other two types are about equally frequent in all ethnic groups. Type II occurs at a rate of 1 in 100,000 live births, while Type III is estimated to occur in 1 in 50,000 live births.
Causes & symptoms
Gaucher disease is caused by the absence, or near absence, of activity of an enzyme called glucocerebrosidase (GC), also known as acid β-glucosidase. The normal action of GC is to break down a common molecule called glucocerebroside. If not broken down, glucocerebroside accumulates in certain cells to levels that can cause damage, especially in the spleen, liver, and bone. The common link among these organs is that they house a cell type called the macrophage (any large cell that surrounds and consumes a foreign substance, such as bacteria, in the body). The cellular structures in which glucocerebroside accumulates are called lysosomes.
Lack of the enzyme is caused by a mutation in the glucocerebrosidase gene. The gene is autosomal, that is, it is located on a non-sex chromosome. It is recessive, meaning that two defective gene copies must be inherited, one from each parent, for the disease to manifest itself.
The results are widespread in the body and include excessive growth of the liver and spleen (hepatosplenomegaly), weakening of bones, and, in acute cases, severe nervous system damage. Many patients experience "bone crises," which are episodes of extreme pain in their bones.
There is a wide array of other problems that occur with Gaucher disease, such as anemia (fewer than normal red blood cells). Just how these other symptoms are caused is not known. Nor is it known why some patients have very mild disease and others have much more significant problems. Even identical twins with the disease can have differing symptoms.
Diagnosis of Gaucher disease, based initially on the symptoms described above, can be confirmed by microscopic, enzymatic, and molecular tests. When biopsy tissue (tissue removed surgically from a problem area) is examined under the microscope, cells will appear swollen and will show characteristic features of the cytoplasm (part of the cell body along with the nucleus) and nucleus. Enzyme assays will show deficiency of the enzyme, GC. Molecular analysis of DNA samples will show structural defects in the gene for GC. Diagnosis can be performed prenatally (before birth) using amniocentesis or chorionic villus sampling.
Diagnosis as to which of the three types of Gaucher disease an individual has is based on the symptoms, rather than on test results.
Until recently, only supportive therapy could be offered. Analgesics are used to control pain. Orthopedic treatment is used for bone fractures. In some cases, surgical removal of the spleen may be necessary.
Several treatments for anemia have been used, including vitamin and iron supplements, blood transfusions, and bone marrow transplants.
The newest form of treatment for Gaucher disease is enzyme replacement therapy, in which GC can be administered intravenously. The enzyme can be prepared either by purification from placentas (alglucerase) or by recombinant DNA manufacturing techniques (imiglucerase). Either way, the cost of treatment is enormous.
Early results indicate that enzyme replacement is effective at reducing most Gaucher symptoms. The notable exception is neurologic damage in type II disease, which remains unimproved by this treatment.
Many questions remain about enzyme replacement therapy in regard to dosage, method, and frequency of administration. The treatment program may need to be crafted individually for each patient.
A patient's expected lifespan varies greatly with the type of Gaucher disease. Infants with type II disease have a lifespan of about two years. Patients with types I and III disease have highly variable outcomes with some patients dying in childhood and others living full lives. Little is known about the reasons for this variability.
No prevention is possible for a genetic condition like Gaucher disease. Genetic counseling is advised for individuals with the disease and for those related to a Gaucher patient.
- Fatty carbohydrates that occur in the brain and nervous system.
- Enzymatic replacement therapy
- This treatment method replaces the missing enzyme. It is possible to synthesize enzymes and then inject them intravenously into patients.
- A cerebroside that contains glucose in the molecule.
For Your Information
- Baranger, John A. et.al. "Enzymatic and molecular diagnosis of Gaucher disease." Clinics in Laboratory Medicine, 15 (4)(December 1995): 899-913.
- Grabowski, Gregory A. "Current issues in enzyme therapy for Gaucher disease." Drugs 52 (2)(August 1996): 159-167.
- NIH Technology Assessment Conference. "Gaucher disease: current issues in diagnosis and treatment." JAMA 275 (7)(February 12, 1996): 548-553.
- Alliance of Genetic Support Groups. 4301 Connecticut Ave. NW, Suite 404, Washington, D.C. 20008. (202) 966-5557, (800) 336-4363.
- National Gaucher Foundation. 11140 Rockville Pike, Suite 350, Rockville, MD 20852-3106. (800) 925-8885. www.gaucherdisease.org.
- National Organization for Rare Disorders. P.O. Box 8923, New Fairfield, CT 06812-1783.
Gale Encyclopedia of Medicine. Gale Research, 1999.