Gaucher disease (GD), an autosomal recessive lysosomal storage disorder, characterized by glucocerebrosidase (GC) deficiency due to mutations in the glucocerebrosidase (GBA) gene. To date, more than 250 mutations have been identified. The aim of present study was to identify sequence alterations in the GBA coding region in GD patients from Brazilian. We have evaluated a group of 125 unrelated patients from a total of over 800 individuals tested that were shown to have GC deficiency through enzyme assay. DNA samples from these patients were analyzed through long-range PCR, followed by specific screening for common mutations and direct sequencing. We have identified common and rare mutations in the mutant alleles. Besides p.N370S and p. L444P, p.G377S mutation was also frequently found in this cohort. Among rare mutations, alterations include insertions, deletions, complex alleles as well as single base changes. In addition, we have also described novel sequence variations that are likely to be disease causing mutations. As these sequences alterations are located in conserved residues of the protein or at a splicing site, these changes are likely to be responsible for changes in the structure and/or function of GC. Full screening of GBA gene is relevant to identified additional rare mutations. Forty-two adults with GD-1 stable after ≥3 years of ERT were enrolled. Endpoints were: change from baseline in liver volume (primary) and in spleen volume, haemoglobin concentration and platelet count (secondary). Mean (SD) patients' age was 45.1 (12.7) years and previous ERT duration was 9.5 (4.0) years. Median exposure to miglustat (100 mg t.i.d.) was 658 (range 3-765) days. Thirteen patients discontinued treatment as a result of adverse events (principally gastrointestinal), six for protocolmandated safety criteria for suspected disease progression, one for noncompliance and one withdrew consent. The primary endpoint was met, as the upper 95% confidence limit of mean percent change in liver volume from baseline to End of Treatment was below the noninferiority margin of 10% [−1.1%; 95%CI −6.0, 3.9%; mean (SD) baseline volume 1775 (484) cm3, mean absolute change −47.5 cm3 (95%CI −151, 56)]. Baseline values [mean (SD)] for spleen volume, haemoglobin concentration and platelet count were 510 (372) cm3, 14.8 (1.6) g/dL, and 198.9 (95.7) W10(9)/L, respectively. Mean (95%CI) absolute changes in these three parameters, respectively, were 102 (24,180) cm3, 0.95 (−1.38,-0.53) g/dL, and 44.1 (57.6, 30.7) W10(9)/L. Miglustat is a useful option for maintenance treatment in patients with GD-1 previously stabilised by enzyme therapy. Conflict of Interest declared. Background: Skeletal involvement is a frequent complication of Gaucher disease (GD), and represents an important cause of morbidity and disability. Objectives: To evaluate retrospectively the long-term efficacy of enzyme replacement therapy (ERT) in correcting bone mineralization in a paediatric cohort of patients with GD type 1. Patients and methods: 18 patients (age 9.2±4.7), receiving ERT (20-60 U/ kg) biweekly, up to a maximum of 17 years, were included. Bone symptoms, growth, imaging and lumbar bone mineral density (BMD) were assessed. Results: At baseline BMD was pathological (Z-Score range: -3.80 to −2.21) in 7/9 patients who started ERT after pubertal spurt, 5 of them showed growth delay. After 2 years of ERT, BMD significantly improved in 13/18 patients: mean values from −1.3 to −1.0 (p=0.02). A significant difference was found between baseline and last reading data (p=0.01). At the end of the study BMD normalized in all but 2 splenectomized siblings; growth delay normalized in all patients. Conclusions: ERT started in paediatric age correct osteopenia, maintain normal BMD and growth in the vast majority of patients (16/18). The improvement of BMD is mainly achieved during the first 2 years of treatment. Early splenectomy may hamper a normal bone mineralization.