Gaucher Disease

Glucocerebrosidase deficiency; Glucosylceramidase deficiency

Gaucher disease affects an estimated 1 in 50,000 to 1 in 100,000 people in the general population. Persons of Eastern and Central European (Ashkenazi) Jewish heritage are at highest risk for the disease.

It is an autosomal recessive disease. This means that the mother and father must both pass one abnormal copy of the gene to the child in order for the child to develop the disease. A parent who silently carries an abnormal copy of the gene is called a carrier.

The lack of the glucocerebrosidase enzyme causes harmful substances to build up in the liver, spleen, bones, and bone marrow. The substances prevent cells and organs from working properly.

There are three main subtypes of Gaucher disease:

• Type 1 disease is most common. It involves bone disease, anemia, an enlarged spleen and thrombocytopenia. Type I affects both children and adults. It is most common in the Ashkenazi Jewish population.
• Type 2 disease usually begins in infancy with severe neurologic involvement. This form can lead to rapid, early death.
• Type 3 disease may cause liver, spleen, and brain problems. Patients may live into adulthood.

Symptoms vary depending on the type of disease, but may include:

• Bone pain and fractures
• Cognitive impairment
• Easy bruising
• Enlarged spleen (splenomegaly)
• Enlarged liver (hepatomegaly)
• Fatigue
• Heart valve problems
• Lung disease
• Seizures
• Severe swelling (edema) at birth
• Skin changes

The doctor will perform a physical exam. The patient may have signs of liver and spleen swelling, bone changes, lung disease, eye movement problems, heart problems, or hearing loss.

The following tests may be performed:

• Blood test to look for enzyme activity
• Bone marrow aspiration
• Biopsy of the spleen
• MRI
• CT
• X-ray of the skeleton
• Genetic testing

Enzyme replacement therapy is available. A bone marrow transplant may be needed in severe cases.

How well a person does depends on the subtype of the disease. The infantile form of Gaucher disease may lead to early death. Most affected children die before age 5.

Adults with the type 1 form of the disease can expect normal life expectancy with enzyme replacement therapy.

• Seizures
• Anemia
• Thrombocytopenia
• Bone problems

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 the Gaucher disease. A prenatal test can also tell if the fetus has Gaucher syndrome.

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Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. 7th ed. St. Louis, Mo: WB Saunders; 2005:163-165.

Sidransky E, Lamarca ME, Ginns EI. Therapy for Gaucher disease: Don't stop thinking about tomorrow. Mol Genet Metab. 2007 Feb;90(2):122-5. Epub 2006 Nov 3.