Genetics and Gaucher Disease

Gaucher disease is an autosomal recessive disorder caused by the presence of two mutant alleles coding for the glucocerebrosidase gene on chromosome 1. To date, more than 300 mutant alleles have been identified,[1] coding for deficient and/or defunct enzymes with decreased stability, decreased binding affinity or other abnormality.[2] The clinical features and course of this monogenetic disease can still vary considerably among patients with the same genotype and phenotypic expression may be different between monozygotic affected twins. [3] Which ‘epigenetic’ factors play a role is largely unknown.

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.[3] The four most commonly identified allele mutations account for 89% to 96% of those in the Ashkenazi population.[4]

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 and a 25% chance that the child will neither be affected nor be a carrier.[5]

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

(Fig. 1) Gaucher disease is not a gender linked disorder. Both males and females can be carriers and affected with Gaucher disease.

Genetic counseling and testing

People at risk of being carriers may want to consider genetic counseling and family DNA testing. Individuals at risk include: first-degree relatives of Gaucher disease patients, persons of Ashkenazi Jewish descent, and symptomatic individuals. Among populations with more consanguineous marriages, wider family screening may be appropriate. Knowledge of carrier status may affect reproductive choices and aid decisions about additional family testing and counseling. [2]

For more information about genetic counseling, visit the website of the US National Society of Genetic Counselors or contact your local clinical genetics center.


1. Koprivica V, Stone DL, Park JK, Callahan M, Frisch A, Cohen IJ, et al. Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease. Am J Hum Genet 2000; 66:1777-86

2. Beutler E, Grabowski GA. Gaucher disease. In: Scriver C, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001:3635-3668.

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

4. Grabowski G. Gaucher disease: enzymology, genetics, and treatment. In: Harris H, Hirshchorn K, eds. Advances in Human Genetics. New York, NY: Plenum Press; 1993; 21:377-441.

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

Did You Know?

Gaucher disease was first described in 1882 by French physician, Philippe Charles Ernest Gaucher, after he evaluated a deceased 32-year-old woman with an enlarged spleen, one of the disorder's distinguishing signs.

Gaucher Registry

For more than a decade, the Gaucher Registry has been a global resource to the medical and patient communities, helping to improve outcomes in patients with Gaucher disease. Learn more about participating in the Gaucher Registry »