What is the age at onset of Gaucher disease and life expectancy?

Symptoms of Gaucher disease Type 1 are variable and may present at any stage of life, or patients may be asymptomatic throughout life.1 From the Gaucher Outcome Survey in 2017, where the majority of patients (91.5%; n=1106/1209) were diagnosed with Gaucher disease Type 1, the median age at diagnosis was 40.4 years (age interquartile range, 26.5‒56.8 years).2 From the International Collaborative Gaucher Group (ICGG) Gaucher Registry, the mean life expectancy at birth of patients with Gaucher disease Type 1 has been reported as 68.2 years (63.9 years for splenectomised patients and 72.0 years for non-splenectomised patients), compared with 77.1 years in a reference population (>5000 phenotypically similar patients worldwide).3

For patients with Gaucher disease Type 2, severe neurological abnormalities are often present before the age of 6 months.4,5 In one French study (n=15), the first symptoms of Gaucher disease Type 2 occurred before 9 months of age (mean age, 3.5 months; age range, 0‒19 months, and in some cases (n=9), symptoms were evident from the first few days of life. For children with Gaucher disease Type 2, the mean age at death in this study was 11.7 months (age range, 2‒25 months).

In most cases of Gaucher disease Type 3, symptoms are evident before patients are 20 years old.1 Results from the ICGG Neurological Outcomes Subregistry in 2010 indicated that of 131 patients enrolled in the study, the mean (standard deviation [SD]) age at diagnosis was 3.2 (6.2) years. For many patients (47%; n=61/131), neurological manifestations of the disease were present before the patient was 2 years old. However, these symptoms were not evident for 41% of patients (n=54/131; data missing for 16 patients) until they were older than 2 years.6

Effect of genotype on age at onset of Gaucher disease: population-based study from the ICGG Gaucher Registry

In cases of Gaucher disease Type 1, data from the ICGG Gaucher Registry indicated that overall mean age at disease onset (defined as age at onset, at diagnosis, or at recognition) for patients was 20.4 years. This analysis reported that 48% were diagnosed before the age of 6 years; 68% were diagnosed between the ages of 0 and 10 years; and 56% were diagnosed between the ages of 10 and 20 years. The age at onset of Gaucher disease can also be affected by specific genotypes (Figure 1).7

The mean age at onset of Gaucher disease across genotypes was reported as follows7:

  • 17.4 years for N370S*/OTHER (n=638)
  • 30.1 years for N370S*/N370S* (n=798)
  • 18.6 years for N370S*/L444P (n=413)
  • 10.9 years for N370S*/84GG§ (n=200)
  • 7.44 years for L444P/OTHER (n=73)
  • 2.76 years for L444P/L444P (n=81).

Figure 1.
Absolute number of patients with onset of Gaucher disease Type 1 (A) and the proportion of patients with a specific genotype (B) presenting in specific decades of life from the ICGG Gaucher Registry. Reproduced with permission from Grabowski GA et al. Am J Hematol 2015; 90: S12-S18.7

*c.1226A>G; p.Asp409Ser
Refers to private or unique alleles7
c.1448T>C; p.Leu483Pro
§c.84dup; pLeu29AlafsTer18

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