Gaucher disease (GD), has a pan-ethnic distribution with incidence in non-Ashkenazi Jewish population about 1/70-140 thousand inhabitants. The deficiency in lysosomal acid beta-glucosidase enzyme secondary to variants in the GBA gene with autosomal recessive inheritance gives rise to a variable clinical picture. It appears at any age with symptoms that include anemia, thrombocytopenia, pain and vascular bone lesions, visceral enlargement, persistent fatigue. It was the first EDL to have enzymatic replacement and substrate reduction therapy that impact in the awareness of the disease. In 1993, the Spanish Registry of Gaucher Disease was created (REsEG), within the Spanish Foundation for the Study and Therapeutics of EG (FEETEG), with the aim of providing support to all those involved in the management of patients with EG and summarize experience at the national level. This work review the characteristics at diagnosis of type 1 adult GD (GD1) patients, diagnosed outside active early diagnosis programs, along of twenty five years of REsEG existence focus on leading diagnostic symptoms in order to answer the current challenges in patients suspicions. Aim: To analyze the evolving profile of GD1 patients diagnosed before and after 2000 based on the principal manifestations including visceral, hematological involvement, bone pain, bleeding in order to define the current suspicious characteristics in our population. Methods: Patients 18+ years old included in the REsEG were selected. Demographic, genetic, clinical (hematological, visceral, bone, neurological) data, severity index, biomarkers and other relevant information were included in a database created for this purpose. Platelets <140x109/L were considered as thrombocytopenia and hemoglobin below 12 g/dL in females and 13 g/dL in males were considered as anemia. Ethic board of SpRGD and FEETEG approved the development of the present work. To analyze the evolution in the diagnostic features of adult GD1 patients, a cut-off settled according the year of diagnosis, <2000 or 2000+, was used. The use of this cut-off was made considering the awareness for diagnostic increased progressively since ERT availability in mid 90's in Spain. The statistical analysis were made using comparative methods with a level of 95% interval of confidence. Results: Since 1993 a total of 223 GD1 with 18+ years old patients were diagnosed and included in the registry. 50.7% (113) were females, mean age at diagnosis 38.5 (18-87). The symptoms that led to the diagnostic of GD1 were: splenomegaly 71.1%, (3 of them detected during pregnancy work out), thrombocytopenia 83.3%, isolated anemia 39.0%, pancytopenia 8.5%, hepatomegaly 22.5%, bone pain: 57.9%(bone crisis 48.8% pathological fractures 3 cases), hemorrhagic diathesis (ecchymosis, epistaxis): 20.6%, peripartum bleeding: 3 cases, family study: 19.3%, early Parkinson's study 3 cases, other reasons for referral were MGUS 4 cases, hyperferritinemia 7 cases. Also we have recorded that bone marrow aspiration or biopsy was the first test in the diagnosis process in about 80% of cases. According the year of diagnosis 131 (58.7%) patients were diagnosed before 2000 (group A), mean age at diagnosis 36 (18-87) y.o and 92 (41.3%) after 2000 (group B). mean age at diagnosis 41.8 (18-79) y.o. General characteristics and genotype distribution are detailed in tables 1 and 2. Concerning profile's patient diagnosed before 2000 showing a more clinical aggressive behavior, even the presence of thrombocytopenia was similar in both groups, the severity of thrombocytopenia were higher in group A (69.8; 16-129 x109/L) vs group B (83.4; 14-131 x109/L) (p=0.006), also anemia, bone pain and visceral enlargement show higher incidences. During this time there 7 cases have developed Parkinson's disease, 2 patients with de novo mutations, 21 neoplasms and other interesting findings. Conclusion: In our population we have found that the classical main characteristics of GD1 adult patients at diagnosis has evolved to a less severe phenotype in the present century. Features like bone pain, anemia, thrombocytopenia, visceral involvement are decreasing in percentage and severity; in parallel mild genetic variants were more prevalent. These data suggest that we need to continue the efforts on training in young hematologist to increase the awareness and visibility of disease, also among primary care providers in order to improve the early diagnosis.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.