Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder resulting from deficiency of beta-glucosidase and accumulation of glucocerebroside in the reticuloendothelial cells. Prevalence of GD is elevated in Ashkenazi Jewish population (1/450-1/1000), and rare in the non-Ashkenazi (1/40000-1/60000). GD is a multisystemic disease; cytopenias and splenomegaly are frequently the presenting symptoms leading to hematological evaluation. Data from the Gaucher Registry 2008 show that splenomegaly and thrombocytopenia are present at diagnosis in more than 5000 patients (respectively 86% and 60%). Because of the non-specific presenting symptoms, diagnostic delays are frequent, leading to severe complications, including hematological malignancies. Enzyme replacement therapy is available and effective in reversing or preventing many manifestations (Weinreb 2002). A global survey among 406 Hematology-Oncology specialists demonstrated that only 20% consider GD in the differential diagnosis of cytopenia, hepatosplenomegaly, and bone pain (Mistry 2007). It is clear that a different approach based on a specific diagnostic algorithm is necessary to avoid under-diagnosis (Mistry 2010).


The aim of this multicenter observational study is to evaluate the prevalence of GD in a selected population presenting to hematological clinic with at least one of the including criteria: 1) splenomegaly, or 2) thrombocytopenia associated to at least one of the following signs: anemia (Hb<11 g/dl in women, and Hb<12 g/dl in men), MGUS, policlonal gammopathy in patient younger than 30 yrs, splenectomy or history of bone pain. Exclusion criteria are: a) portal hypertension in chronic liver disease, b) hematological malignancy, c) hemoglobinopathies or other hemolitic anemias.


Thirty-five Italian Hematologic Centers participate in this study. According to a preliminary survey, among all the first hematological evaluations per year (mean of 1100 evaluations per center), the 18% (198) was positive for splenomegaly and/or thrombocytopenia; among them the 11% (21.7) did not receive a diagnosis. Based on these results, 762 (35 x 21.7) patients were expected to be tested every year. Patients fulfilling including criteria who have given their informed consent were recruited into the study and tested for beta-glucosidase enzyme activity on Dried Blood Spot (DBS). DBS-based approach, set up by Olivova et al. (Olivova 2008), was firstly validated by conventional enzymatic testing on 25 GD patients’ and 25 (out of 250) controls’ samples. All the analysis are centralized and performed at Gaslini Institute, Genoa. Results showing decreased or borderline beta-glucosidase activity (cut off=12.42±8.2 pmol punch-1 h-1) require conventional diagnostic approaches which include enzymatic genetic testing in the leukocytes from fresh blood and cell lines (Epstein-Barr virus–transformed lymphoblasts from blood or fibroblasts from skin biopsy), and in the case of diagnosis confirmation, the molecular genetic analysis. The expected duration of the study was 24 months, starting from September 2010, subsequently extended up to the enrolment of 500 patients (recruitment still active at present).

Data are collected and analyzed at Rare Disease Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan. We compared clinical, hematological and biochemical parameters between patients affected and unaffected by GD with Wilcoxon rank-sum (Mann-Whitney) test.


Starting from September 2010, 180 patients (55 females, 125 males) have been enrolled. The mean age of patients was 49.2±18.1 yrs; all the patients are non-Ashkenazi. The inclusion criteria were splenomegaly alone in 114 patients, thrombocytopenia alone in 7 patients and both of them in 59 patients. Six (3.4%) patients were diagnosed with GD. The mean age at diagnosis was 32.6±8.6 yrs. Among clinical and laboratory parameters, only mean serum ferritin was significantly increased in patients affected by GD (660±541 ng/ml, range 1457-294) compared to non-GD patients (229±269 ng/ml, range 1500-5, p=0.02).


The use of a simple diagnostic algorithm helps to identify GD patients presenting to haematologists. These results are clinically relevant because an early diagnosis of GD leads to an appropriate and prompt therapy to prevent the development of complications.


No relevant conflicts of interest to declare.