Gaucher Disease (GBA)

Gaucher disease is an autosomal recessive disease caused by pathogenic variants in the gene GBA. While it is found in populations worldwide, it is most prevalent in individuals of Ashkenazi Jewish descent. Gaucher disease has variable clinical features and can be divided into the following subtypes. Type 1 is characterized by bone disease and the lack of neurological involvement. The bone disease can vary in severity from asymptomatic to destruction of bone tissue and painful bone crises. Patients often have anemia and abnormal blood cell counts and may have lung disease. Some patients may be asymptomatic. Type 2 is a severe form that begins in infancy and usually results in death by the age of 2 years. It is characterized by severe neurologic deterioration, seizures, anemia, poor feeding and failure to thrive. The perinatal-lethal form is a more severe subtype of type 2, where accumulation of fluid in the fetus results in death in utero, or in the first several days of life. Some patients do not have the excess fluid, but die within three months. Type 3 is characterized by neurologic deterioration, as with type 2, but onset may be anywhere from childhood to adulthood, and progresses more slowly. Patients develop seizures and declining intelligence. Patients also experience the bone disease and anemia seen in type I. The cardiovascular form is a subtype of type 3 that is characterized by calcification of the heart valves during adolescence. Patients may also have problems controlling their eye movements. The cardiac manifestations are usually fatal. Some pathogenic variants are associated with a specific type of Gaucher disease. However, there is significant variability in the phenotypes, even between identical twins. Therefore, it is not always possible to predict the severity of disease based on genotype.









Disease Name
 GeneGuaranteed Exons 
 Inheritance Ethnicity
 Carrier Frequency
 Detection Rate
Residual Risk

Gaucher DiseaseGBAp.L29fs, c.115+1G>A, p.N409S, p.L422fs, p.V433L, p.D448H, p.D448V, p.L483P, p.R502C, p.R502H, p.R535CARCaucasian1 in 16467%0.00202020202020202
Gaucher DiseaseGBAp.L29fs, c.115+1G>A, p.N409S, p.L422fs, p.V433L, p.D448H, p.D448V, p.L483P, p.R502C, p.R502H, p.R535CARAshkenazi Jewish1 in 15>95%0.00355871886120996
Gaucher DiseaseGBAp.L29fs, c.115+1G>A, p.N409S, p.L422fs, p.V433L, p.D448H, p.D448V, p.L483P, p.R502C, p.R502H, p.R535CARWorldwide1 in 15856%0.00279329608938547