Clinical, Genetic Characteristics and Geographical Distribution of Gaucher Disease In Iberian Peninsulae and Islands

The actual population of Iberian Peninsula (IP) is about 55 millions of inhabitants with a combination of various ethnic groups There are several reports that have analyzed GBA mutations in specific IP population. The aim of this study is to describe the distribution and main clinical characteristics of GD patients in IP.

Data from the National Spanish Gaucher Disease Registry, Genetic Department of Barcelona University and Genetic Medical Institute of Porto since 1970 were jointed. Statistical analysis of demographic data, geographical distribution of GBA mutations and allelic frequency of GBA mutations in IP were analyzed. As well as identified the existence of clusters and the distribution of different types, the type and years on therapy. In addition we have determined the age at diagnosis (aDx) and SSI.

The prevalence of GD in IP had been 436 diagnosed patients, 421 of them born in IP. The mean aDx was 26.3±19.88 y, there are not differences between aDx before and after the last decade (24.8 vs 26.9 years respectively). Gender: female: 47.74 %, male: 47.98%, unknown: 4.28% type 1: 375 (89.1%), type2: 27(6.4%), type3: 19(4.5%). Mean SSI in type1 GD was 7.7 (range 1–30), and the distribution was 72.7% mild, 25.5% moderate and 1.7% severe. We have identified 70 alleles and 76 different mutations. The most prevalent allelic frequencies were: N370S: 48.8%, L444P: 18.3%, D409H: 3.1%, G3877S: 2.9%, double mutation: L444P+E326K: 2.0%, which account the 75% of total alleles, in 3.3% of alleles the mutation has not been yet identified and the remaining alleles corresponding to private mutations. Nevertheless the most frequent IP genotypes were N370S/L444P, 27.8%, N370S/N370S, 15%, N370S/? 5.2%, G377S/D409H, N370S/G202R, N370S/c.84insG, 2.4% respectively and homozygous for L444P 2.1%. Both Spain and Portugal the most prevalent mutations were N370S and L444P, however N370S is more frequent in Portugal than in Spain (57.1% vs 46.5%) by contrast L444P is more frequent in Spain than Portugal (19.4% vs 14.3%). 247 patients (58.7%) have received ERT for a mean of 10.2±3.89 years and 53 (12.6%) has been treated with miglustat for a mean of 2.1±1.9 years. The 90.4% of type1 and 31.0% of type 3 are alive and all type 2 are dead.

There are broad spectrums of GBA mutations in GD patients from IP. Five different mutations account for 75% of GBA mutant alleles including N370S, L444P, D409H and G377S. No differences in gender distribution and tendency of aDx were observed. The 98.2% of type1 GD has a mild or moderate grade of severity and 23.0% has never received ERT or SRT.

No relevant conflicts of interest to declare.