Gaucher disease is an autosomal recessive disorder defined by the presence of two mutant alleles for the glucocerebrosidase gene. To date, more than 200 mutant alleles have been identified,^[1] which have been found to code for enzymes with either decreased stability or decreased binding affinity.^[2] The clinical features and course of the disease can vary among patients with the same genotype.^[1]

The Ashkenazi connection

Although Gaucher disease is panethnic, the incidence rate is relatively high (as many as 1 in 850 people) among individuals of Eastern European (Ashkenazi) Jewish descent, with a carrier frequency of 1 in 12 to 15 Ashkenazi Jews.^[1,3,4]. The four most commonly identified allele mutations account for 89% to 96% of those in the Ashkenazi population,^[5]

A Young Couple's Guide to Jewish Genetic Disorders and Screening (PDF)

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The odds of transmitting Gaucher disease

With each pregnancy, each carrier has a 50% chance of passing along a mutated gene. When both parents are carriers, there is a 25% chance with each pregnancy that the child will develop Gaucher disease.^[8]

The diagrams below show how the Gaucher gene can be passed from one generation to the next.

Genetic counseling and testing

People at risk of being carriers may want to consider genetic counseling and family DNA testing. Individuals at risk include: relatives of Gaucher disease patients, persons of Ashkenazi Jewish descent, and symptomatic individuals. Knowledge of carrier status may affect reproductive choices and aid decisions about additional family testing and counseling.^[6,7]

For more information about genetic counseling, visit the website of the National Society of Genetic Counselors.

1. Grabowski GA. Lysosomal storage diseases. In: Braunwald E, Fauci AS, et al, eds. Harrison’s Principles of Internal Medicine. 15^th ed. New York, NY: McGraw-Hill; 2001:2276-2281.

2. Beutler E, Grabowski G. Gaucher disease. In: Scriber CR, Beaudet AL, Sly WS, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 7^th ed. New York, NY: McGraw-Hill; 1995;2:2641-2661.

3. National Center for Biotechnology Information. Genes and disease. Available at: http://www.ncbi.nlm.nih.gov/disease/Gaucher.html. Accessed May 2, 2002.

4. Zimran A, Gelbart T, Westwood B, et al. High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews. Am J Hum Genet. 1991;49:855-859.

5. Grabowski G. Gaucher disease: enzymology, genetics, and treatment. In:Harris H, Hirshchorn K, eds. Advances in Human Genetics. New York, NY: Plenum Press; 1993:377-441.

6. Morales LE. Gaucher’s disease: a review. Ann Pharmacother. 1996;30:381-388.

7. National Library of Medicine. Medical encyclopedia: Gaucher disease. Available at: www.nlm.nih.gov/medlineplus/ency/article/000564.htm. Accessed August 5, 2002.

8. Jameson JL, Kopp P. Principles of human genetics. In: Braunwald E, Fauci AS, et al, eds. Harrison’s Principles of Internal Medicine. 15^th ed. New York, NY: McGraw-Hill; 2001:375-396.