1st Pediatric Clinic, Center of Genetic Diseases, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj, Romania.
Eur J Intern Med. 2010 Apr;21(2):104-13. doi: 10.1016/j.ejim.2009.11.005. Epub 2009 Dec 6.
BACKGROUND/AIM: To present clinical and genetic characteristics of all Romanian patients with Gaucher disease type 1, in whom specific diagnosis has been confirmed by enzymatic and molecular methods and to analyze their outcome with and without enzymatic replacement therapy (ERT).
PATIENTS, METHODS: There are fifty patients (F/M - 1.63/1) with Gaucher disease type 1. Clinical status, haemoglobin, thrombocytes, hepatic/splenic volume, bone mineral density and severity score were assessed at baseline and every six months thereafter. Thirty-nine patients (78%) received imiglucerase (44.4+/-13.6 U/kg/2 weeks) for 3.1+/-1.4 years.
Based on general prevalence data, our group represents 22.7% of the expected total number of patients with Gaucher disease type 1 in Romania. Mean age was 15.5 years at clinical onset and 28.9 years at confirmation of diagnosis. The genotype N370S/L444P was frequent in our group (35.9% of alleles). Anaemia, thrombocytopenia, splenomegaly and bone disease were present at 38%, 70%, 100% and 84%, respectively. Mean values for haemoglobin, thrombocytes, hepatic volume and chitotriosidase normalized after 0.5, 1.5, 2.5 and 3 years of ERT, respectively. Splenomegaly regressed from 14.4 x N (normal) to 3.06 x N over four years of treatment. Bone disease was ameliorated under ERT, yet bone mineral density worsened in patients treated with 30 U/kg/2 weeks.
The genotype N370S/L444P is frequent in our patients, in line with the severe phenotypes. ERT improved haematological parameters and visceromegaly, without a clear benefit for bone mineral density. To attain therapeutic goals, an early treatment start with optimal dosage is mandatory.
背景/目的：介绍所有罗马尼亚 1 型戈谢病患者的临床和遗传特征，这些患者通过酶学和分子方法明确诊断，并分析他们在接受和不接受酶替代治疗（ERT）时的结果。
有 50 名 1 型戈谢病患者（F/M-1.63/1）。在基线时和此后每 6 个月评估临床状态、血红蛋白、血小板、肝/脾体积、骨矿物质密度和严重程度评分。39 名患者（78%）接受伊米苷酶（44.4+/-13.6 U/kg/2 周）治疗 3.1+/-1.4 年。
基于一般流行数据，我们的组代表了罗马尼亚预期的 1 型戈谢病患者总数的 22.7%。临床发病时的平均年龄为 15.5 岁，确诊时的平均年龄为 28.9 岁。我们组中频繁出现 N370S/L444P 基因型（35.9%的等位基因）。贫血、血小板减少、脾肿大和骨病的发生率分别为 38%、70%、100%和 84%。ERT 后血红蛋白、血小板、肝体积和壳三糖苷酶的平均数值分别在 0.5、1.5、2.5 和 3 年时正常化。脾肿大从治疗前的 14.4 x N（正常）缩小到治疗 4 年后的 3.06 x N。骨病在 ERT 下得到改善，但在接受 30 U/kg/2 周治疗的患者中骨矿物质密度恶化。
我们的患者中频繁出现 N370S/L444P 基因型，与严重表型一致。ERT 改善了血液学参数和内脏肿大，但对骨矿物质密度没有明显益处。为了达到治疗目标，必须尽早开始用最佳剂量进行治疗。
