Gaucher disease is an inherited deficiency of the enzyme glucosidase, which results in the buildup of a toxic substance (glucosylceramide) in different parts of the body, such as the spleen, liver, and bones.

Glucocerebrosidase Deficiency; Glucosylceramidase Deficiency

Gaucher Disease is an inherited disorder that affects an estimated  1 in 50,000 to 1 in 100,000 people in the general population. Individuals of Eastern and Central European (Ashkenazi) Jewish heritage are at higher risk for being affected.

Deficiency of the enzyme glucocerebrosidase causes the lysosomes to become congested with glucosylceramide. These congested lysosomes buildup in the liver, spleen, bones, and bone marrow. This, in turn, leads to decreased production of red blood cells (anemia), and thinning of the bones (osteopenia).

It is an autosomal recessive disease. This means that an affected child would inherit two abnormal copies of the enzyme, one from the mother and one from the father. The parents are known as carriers since they do not have the disease, but silently harbor one abnormal copy of the gene.

There are five subtypes of  Gaucher Disease.

• Type 1 disease is most common. It is characterized by bone disease, anemia, an enlarged spleen and thrombocytopenia. Type I affects both children and adults. It is most prevalent in the Ashkenazi Jewish population, affecting anywhere from 1 out of 500-1,000 births.
• Type 2 disease usually begins in infancy with severe neurologic involvement. This form can lead to rapid, early death.
• Type 3 disease typically is marked by primary neurologic involvement and runs a slower, more favorable course.
• Type 4 is a marked by dry, rough, scaly skin and severe edema upon birth, and is deadly.
• Type 5 is a cardiovascular form characterized by calcification of  heart valves, a mildly enlarged spleen, and eye problems.

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

• enlarged spleen (splenomegaly)
• enlarged liver (heptomegaly)
• lung disease
• skin changes
• cognitive impairment
• bone pain and fractures
• easy bruising
• fatigue
• seizures
• severe edema at birth
• heart valve problems

The following tests may be performed:

• blood cell examination for decreased enzyme activity
• white blood cell cultures for beta-glucosidase
• bone marrow aspiration
• biopsy of the spleen
• MRI, CT and/or X-ray of the skeleton
• Genetic testing. This is performed by obtaining bone marrow or blood. Genetic testing may be used to confirm blood tests, test for carrier status, to make a prenatal diagnosis, and to determine prognosis.

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

For more information contact:

• National Gaucher Foundation: www.gaucherdisease.org
• Chicago Center for Jewish Genetic Disorders: www.jewishgeneticscenter.org
• Gauchers Association: www.gaucher.org.uk

Prognosis depends on the subtype of the disease. The infantile form of Gaucher disease may lead to early death. Most affected children die before the age of 5 years. With the availability of synthetic enzyme, most patients with the adult-chronic form can look forward to normal or near-normal life expectancy.

• seizures
• anemia
• thrombocytopenia
• bone infarctions

Call your health care provider or a Comprehensive Gaucher Center if you have a family history of Gaucher disease.

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.