Report of the Spanish Gaucher's Disease Registry: clinical and genetic characteristics

Background and Objectives. Since 1993 the demographic, clinical, analytical , genetic and follow-up data of Spanish patients with Gaucher's disease (GD ) have been collected in an anonymous national database. Some statistical a nalyses of these data are reported concerning the distribution, clinical an d :genetic characteristics of GD in Spain and the response to enzyme replac ement therapy (ERT) is evaluated. Design and Methods. We performed a cohort study in Spanish GD patients by n ational inquiry, submitted by mail to 75 Spanish hospitals lover 300 beds) directed to internal medicine, hematology and pediatric departments. The qu estionnaire included 30 questions (gender, height, weight, date of birth, d ate of diagnosis, abode and number of relatives affected, bone crises, neur ologic symptoms, other symptoms, liver and spleen size, hemoglobin, leukocy te and platelet count, tartrate resistant acid phosphatase, ALT/AST, chitot rioxidase activity, total plasma chotesterol, triglycerides, high density l ipoprotein cholesterol, enzymatic activity of acid P-glycosides, mutation, X-ray examination, magnetic resonance imaging-MRI-evaluation, spleen remova l, and orthopedic procedures (ERT, date of first infusion). Each case with a presumed diagnosis was considered an enrolled patient. Written informed c onsent was obtained from all patients. The cases without enzymatic or genet ic diagnosis were studied in a reference laboratory (the same for all the s amples). Clinical status was evaluated by Zimran's severity score index. Th e enzymatic activity of acid P-glycosides was determined in cellular extrac ts of peripheral blood granulocytes by a fluorescent method using an artifi cial substrate (4-methyl-umbelliferyl beta-D-glycoside). Polymerase chain r eaction [PCR) molecular analysis was performed in DNA samples to characteri ze the mutations (N370S, L444P, IVS2+1, 84GG, D409H, R463C and G377S) of th e glycoside genes. Two groups were created according to age at diagnosis: c hildren under 15 years and adults, in : order to evaluate clinical, genetic s and follow-up. Effectiveness of ERT was evaluated using objective paramet ers (hemoglobin, platelets, liver and spleen size, skeletal lesions), befor e and after therapy. In patients under ERT, quality of life (QOL) was asses sed by a SF-36 modified inquiry, including 22 questions. Statistical analys is including descriptive and frequency distribution for each variable was p erformed, the ANOVA test was used to identify differences between groups. P aired t-tests (before and during therapy) were carried out. The degree of l inear association among measured variables was estimated by Pearson's corre lation. Results. By December 1999 one hundred and fifty-five patients from 117 fami lies had been included from 66 Spanish Hospitals; the inquiry was complete for 114 patients. Mean age at diagnosis: 24.0+/-16.9 years, M/F: 72/83, No symptoms were present at diagnosis in 19.3%; visceral disease was present i n 95.6% and bone disease in 62.4%. Hemoglobin levels, leukocyte and platele t counts were below the normal range in 62.3% of cases. Higher acid phospha tase levels were observed in 99% of cases; biochemical liver dysfunction te sts were found in 42.9%. The test for acid glycosidase showed a marked decr ease in enzymatic activity. Morphologic documentation (spleen or liver tiss ue, bone marrow biopsy or aspirate) of GD was obtained in 71% of the patien ts. The most frequent mutations observed were N370S [46.3% of the alleles d etected), and L444P (18.5%). In 18.7% of the cases the disease was stable o r progressing slightly; in 23.8% the spleen had been removed between 1-14 y ears after diagnosis and 60.6% were under ERT. Children showed both greater liver enlargement and higher SSI (p = 0.0001). There was a correlation bet ween SSI and clinical or analytical data in adults patients for spleen size (Z: 3.142; CI: 0.173-0.637; p= 0.0017). In 35 patients on ERT, clinical an d analytic data improved as did self-evaluated QOL (p< 0.0001). Interpretation and Conclusions. In conclusion, clinical characteristics of Gaucher's disease in Spain were similar to those in other non-Jewish popula tion. N370S allele is the most frequent mutation identified. ERT clearly co ntributes to improving QOL and clinical manifestations. (C)2000, Ferrata St orti Foundation.