What is the prevalence of Gaucher disease in the Ashkenazi Jewish population?

The prevalence of Gaucher disease Type 1 is higher in individuals with Ashkenazi Jewish ethnicity, with a birth incidence of approximately 1 in 850.1,2 Due to the scarcity of reported cases, Gaucher disease Type 2 has been described as rare in the Ashkenazi Jewish population and is phenotypically similar to the disease in other ethnic groups.3 Results from the Gaucher Outcome Survey (GOS), an international Gaucher disease registry established in 2010 for patients with a confirmed diagnosis of Gaucher disease (regardless of type or treatment status), indicated that of the 498 patients of Ashkenazi Jewish ethnicity, only 0.9% had Gaucher disease Type 3 (vs 96.6% with Gaucher disease Type 1; data missing for 2.4% of patients).4

Furthermore, data from the GOS showed that of the 1209 patients who had enrolled as of 25 February 2017, 44.3% (n=536) were from Israel, and of these, 92.9% (n=498) were Ashkenazi Jewish. For the remaining patients of Ashkenazi Jewish ethnicity, 172 were from the US, three were from the UK and two were from the rest of the world (which includes Argentina, Brazil, France, Italy, Paraguay, Poland, Russia and Spain).4 


What is the genetic association between Gaucher disease and the Ashkenazi Jewish population?

The high frequency of Gaucher disease in the Ashkenazi Jewish population is due to the occurrence of a mutation at nucleotide 1226 of GBA1, the gene that encodes glucocerebrosidase (see genetic inheritance of Gaucher disease). This mutation was identified in >75% of alleles from 57 unrelated Ashkenazi Jewish patients with Gaucher disease, and in 8% of alleles from 50 healthy Jewish volunteers.1,5

An analysis of 593 DNA samples from healthy Ashkenazi Jewish participants revealed that the GBA1 N370S (c.1226A>G; p.Asp409Ser) mutation in the heterozygous state was identified in 37 healthy Ashkenazi Jewish volunteers and in two individuals for the homozygous state. This finding indicates that the gene frequency of the N370S (c.1226A>G; p.Asp409Ser) mutation of GBA1 was 0.035 in healthy Ashkenazi Jews. Genetic analysis showed that the N370S (c.1226A>G; p.Asp409Ser) mutation represented 73% of 124 alleles from Ashkenazi Jewish patients with Gaucher disease, indicating a gene frequency of 0.047, which is equivalent to a carrier frequency of 8.9%.1

Frequency and origin of two genetic mutations associated with Gaucher disease in the Ashkenazi Jewish population: a retrospective analysis

A retrospective analysis aimed to verify the frequency and trace the origin of Gaucher disease mutations in patients of Ashkenazi Jewish ethnicity (confirmed by the birthplace of their grandparents e.g. Austria, the Baltic countries, Belarus, Czech Republic, Germany, Hungary, Moldova, Poland, Romania and the European part of Russia). Gaucher disease carrier status in participants was screened between 2006 and 2011, and mutations were identified using restriction analysis of 16,910 Ashkenazi Jewish alleles. A GBA1 mutation was identified in 509 participants, indicating a carrier rate of 1 in 16.6. N370S (c.1226A>G; p.Asp409Ser) and R496H (c.1604G>A; p.Arg535His) mutations were the most frequent in this population; the carrier frequency of these mutations was 1:19.4 and 1:207, respectively. The ratio of NS70S (c.1226A>G; p.Asp409Ser) and R496H (c.1604G>A; p.Arg535His) carriers in Romania to Poland was 0.547 and 1.11, respectively, compared with 0.52 for normal alleles.6*


The prevalence of disease manifestations at any time in patients with Gaucher disease was reported as follows7:

  • 69.6% anaemia
  • 62.0% thrombocytopaenia
  • 40.4% bone event
  • 15.6% splenomegaly
  • 7.4% hepatomegaly
  • 4.0% pulmonary hypertension
  • 3.8% calcification of cardiac valves.


What are the clinical characteristics of patients with Gaucher disease in Israel, where there is a large Ashkenazi Jewish population?

A cross-sectional study was conducted to characterise a population-based cohort of patients with Gaucher disease in Israel (n=500) relative to the general Israeli population (n=4,196,955) in terms of sociodemographic and clinical differences. Using data from electronic health records from the Clalit Health Services, all patients diagnosed with Gaucher disease as of 30 June 2014 were included in the study.7

Among these 500 patients with Gaucher disease, most (90.6%) were aged ≥18 years and 54.0% were female. Although it could not be directly confirmed if these patients were specifically Ashkenazi Jewish, 93.6% did identify their ethnicity as Jewish (vs 73.4% in the general Israeli population).7

*Only two groups of mutated alleles were large enough for statistical analysis of the prevalence among the countries of origin: carriers of N370S (c.1226A>G; p.Asp409Ser) and R496H (c.1604G>A; p.Arg535His) among alleles from Romania and Poland6


C-ANPROM/INT//7566; Date of preparation: September 2020