Mapping the genetic and clinical characteristics of Gaucher disease in the Iberian Peninsula
1 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Zaragoza, Spain
2 Instituto de Investigación Sanitaria de Aragón (IIS), Zaragoza, Spain
3 Spanish Gaucher Disease Foundation (FEETEG), Zaragoza, Spain
4 Barcelona Institut de Bioquímica Clínica (Errores Congénitos del Metabolismo), Hospital Clinic; IDIBAPS, Barcelona, Spain
5 Barcelona Departament de Genètica, Facultat de Biologia, Universitat de Barcelona; IBUB, Barcelona, Spain
6 Portuguese Coordinating Committee for the Treatment of Lysosomal Storage Diseases, CCTDLS (1993-2005), Institute for Molecular and Cell Biology of Porto, Porto, Portugal
7 Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain
8 S° Hematología Hospital Universitario Miguel Servet, P° Isabel La Católica, 1-3 50006 Zaragoza, Spain
Orphanet Journal of Rare Diseases 2012, 7:17 doi:10.1186/1750-1172-7-17Published: 19 March 2012
Gaucher disease (GD) is due to deficiency of the glucocerebrosidase enzyme. It is panethnic, but its presentation reveals ethnicity-specific characteristics.
We evaluated the distribution, and clinical and genetic characteristics of GD patients in the Iberian Peninsula (IP). We analysed geographical distribution, demographic, genetic and clinical data, age at diagnosis, type, and years of therapy in 436 GD patients from the IP.
The prevalence of GD was 1/149,000 inhabitants; 88.3% were type 1, 6.7% type 2, and 5.0% type 3. The mean age at diagnosis in type 1 was 28.7 years. A total of 72.7% were classified as having mild forms, 25.5% moderate, and 1.7% severe. Anemia and thrombocytopenia were present in 56% and 55%, respectively. Bone disease and hepatomegaly were reported in 62% and 68%, respectively, and were more likely in asplenic than in non-splenectomized patients. Sixty-nine mutant alleles were identified, and five mutations accounted for 75% of the GBA alleles. Several patients described in our series had interesting phenotypes. A total of 58.7% of patients had received enzyme replacement therapy and 12.6% were treated with miglustat.
A broad spectrum of GBA mutations is present in the IP, with 98.2% of type 1 GD being mild and 23.0% never treated. These data highlight genetic and phenotypic heterogeneities among geographic populations.