Gaucher disease (Type I)

Gaucher Disease is the most common of the lipid storage diseases. It is caused by a deficiency of the enzyme glucocerebrosidase, which leads to a collection of fatty material in the spleen, liver, kidneys, lungs, brain, and bone marrow. It has three subtypes, with Gaucher Disease Type I being the most prevalent. It is also the most common genetic disease among Ashkenazi Jews in North America. A genetic defect in the enzyme, that normally breaks down the chemical glucocerebroside in the cell, allows this substance to accumulate excessively in the liver, spleen, and lymph nodes, giving rise to the symptoms associated with Gaucher Disease Type I.


Typically, the first sign of this disorder is an enlarged spleen. Anemia, low blood platelets, consequent fatigue, bruising, and a yellow fatty deposit on the white part of the eye are also symptoms. Skeletal weakness and bone disease may occur, leading to collapsed hips, shoulders, and spine.

Inheritance Patterns

Gaucher Disease Type I is an autosomal recessive disorder.

Diagnosis and Testing

A blood or skin test is performed to confirm a diagnosis of Gaucher Disease Type I. This blood test measures the amount of the enzyme glucocerebrosidase and compares it to normal enzyme activity levels. If the disorder is present, low levels of this enzyme will be present as well.  Carrier testing can also be performed. In the Ashkenazi Jewish population, four common mutations (N370S, L444P, 84GG, and IVS2) account for roughly 95% of all nonfunctional Gaucher genes. If a mutation is found, the individual is a carrier. If none of the four mutations are found, there is still a chance that the individual is a carrier because other mutations could be present. A small percentage of non-Jewish individuals carry one of these common mutations.


Enzyme replacement treatment given intravenously every two weeks can dramatically decrease liver and spleen size, reduce skeletal abnormalities, and reverse other manifestations of the disease. For patients who cannot be treated with enzyme replacement therapy, an enzyme inhibiting medication, miglustat, can be taken orally and has demonstrated some benefit.  Successful bone marrow transplantation cures the non-neurological manifestations of the disease. However, this procedure carries significant risk and is rarely performed in Gaucher patients. Surgery to remove the spleen may be required on rare occasions (if the patient is anemic or when the enlarged organ affects the patient’s comfort). Blood transfusion may benefit some anemic patients. Other patients may require joint replacement surgery to improve mobility and quality of life.

Gaucher disease (Type I) results from an enzyme deficiency that causes a fatty substance to accumulate in the liver, spleen, and bone marrow. Symptoms include anemia, easy bruising, impaired clotting, bone and joint pain, and other orthopedic problems.

Symptoms may appear in childhood or much later in life. Some patients may suffer from chronic ill health, while others may experience few, if any, of the disease manifestations.
Enzyme replacement therapy has been developed in recent years and has been highly effective in reversing some symptoms and reducing the severity of others.

Type I Gaucher is the most prevalent Jewish genetic disease, with a carrier frequency of about 1 in 15. Screening will detect approximately 95% of cariers.

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