Disease Information

Clinical Manifestations of Gaucher Disease

There are three subtypes of Gaucher disease. There is a wide variability in the pattern and severity of disease involvement between and within each subtype. All three variants of Gaucher disease are inherited "storage" diseases but are distinguished by the presence or absence of neurologic complications (Table I).

Type I Gaucher Disease

Type I disease is the most common form of Gaucher disease and does not directly involve the nervous system. In the United States, there are estimated to be 20,000 or more patients with Type I Gaucher disease. This disease is the most common genetic disorder in Jewish individuals of Central and Eastern European ancestry (Ashkenazic Jews). Approximately one in eighteen Ashkenazi carry the gene for this disease. However, Gaucher disease is not restricted by geographic or cultural boundaries and has been found in all ethnic groups.

The clinical manifestations usually become apparent in childhood or early adulthood, when patients initially show an enlarged spleen or develop hematologic problems (anemia and/or low platelet count) or orthopedic (bone) complications. Gaucher cells in the bone marrow may lead to symptoms of bone and joint pain, fractures, and other orthopedic problems. Accumulation of Gaucher cells in the spleen and liver leads to enlargement of these organs as well as blood abnormalities such as anemia and thrombocytopenia (low platelet count) with subsequent easy bruisability and impaired blood clotting.

Since there is marked variability in the severity of Type I disease, even among family members, it is difficult to predict the future severity and extent of complications in individual patients. Some patients are severely affected in their teens, while others are relatively asymptomatic when diagnosed in their 50s or 60s. Although there is no "classic" predictable disease course, prognosis generally depends on the severity at diagnosis and the occurrence interval between disease complications in each patient.

Type II Gaucher Disease

Type II disease has its onset in infancy and is a fatal neuro-degenerative disorder with death occurring in the first or second year of life. Extensive liver and spleen enlargement is present, but oculomotor (eye movement) abnormalities may be the first noted findings. Other findings may include rapid head thrusts, bilateral fixed strabismus and or neck muscle hypertonia, limb rigidity, and seizures. It is very rare and does not have a predilection for any particular ethnic or demographic group.

Type III Gaucher Disease

Type III disease is intermediate in severity between Types I and II in that the neurologic symptoms occur but present later and in a milder form than in Type II. The first symptoms are usually the enlargement of the liver and spleen with eventual eye movement disorders. Some patients progress to have further neurologic involvement including dementia, ataxia, and spasticity. The prototype form of this disease has been found in population isolates in northern Sweden. Again, this form of the disease can occur in all ethnic and demographic groups.

Each of these three types of Gaucher disease is genetically distinct and "breeds true" in affected families - that is, the type of Gaucher disease occurring in a specific family remains the same through successive generations.