BACKGROUND Gaucher disease (GD) is caused by functional defects of the acid β-glucocerebrosidase enzyme, with accumulation of glucosylceramide in the macrophage lineage lysosomes causing multisystem abnormalities. However, some GD manifestations can't be explained by Gaucher-cells infiltration. Recent studies emphasized the role of inflammation in GD. AIM To compare the level of TIMP1 (Tissue-inhibitory metalloproteinase-1) and VEGF (Vascular-endothelial growth factor) and nail-fold capillaroscopy (NFC) changes in children and adolescents (CA) with GD and controls and correlate them to disease-severity, genotype, visceral and neurological manifestations. METHODOLOGY Fifty-three CA with GD were compared to 52 age and sex matched healthy controls stressing on ERT (enzyme replacement therapy) dose and duration, pulmonary, hematological and neurological manifestations with assessment of severity-scoring index (SSI). Full neurological, abdominal and chest examinations were done. Sonographic liver and spleen volumes and NFC were assessed. GD genotype was done. Serum TIMP-1 and VEGF were measured. RESULTS CA with GD had significantly higher TIMP-1 (P < 0.001) and VEGF (P < 0.001) than controls. Type 3CA with GD had significantly higher TIMP-1 (P = 0.004) and VEGF (P = 0.035) than type 1. There was a significant positive correlation between TIMP-1 and each of VEGF (P < 0.001), SSI (P < 0.001) and NFC (P < 0.001). A significant positive relation was found between TIMP-1 and convulsions (P = 0.002), dysphagia (P = 0.008), opthalmoplegia (P = 0.038) and developmental delay (P < 0.001). Multi-variate logistic regression analysis for predictors of children and adolescents with GD revealed that its most correlated to TIMP-1 (P = 0.008) and NFC changes (P = 0.025). CONCLUSION Macrophage proliferation in GD modulates local inflammation, micro-angiopathy and neo-angiogenesis. NFC can be used as a noninvasive indicator of microangiopathy in GD.

中文翻译：

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血管内皮生长因子（VEGF）、金属蛋白酶-1 组织抑制剂（TIMP-1）和甲襞毛细血管镜检查在儿童和青少年戈谢病中的变化；与残留疾病严重程度的关系

背景戈谢病（GD）是由酸性β-葡萄糖脑苷脂酶的功能缺陷引起的，葡萄糖神经酰胺在巨噬细胞谱系溶酶体中的积累导致多系统异常。然而，一些GD表现不能用戈谢细胞浸润来解释。最近的研究强调了炎症在 GD 中的作用。目的 比较患有 GD 和对照组的儿童和青少年 (CA) 的 TIMP1（组织抑制金属蛋白酶-1）和 VEGF（血管内皮生长因子）和指甲皱襞毛细血管镜检查（NFC）的变化，并将它们与疾病相关联。严重程度、基因型、内脏和神经系统表现。方法 将 53 名患有 GD 的 CA 与 52 名年龄和性别匹配的健康对照进行比较，强调 ERT（酶替代疗法）剂量和持续时间、肺、血液学和神经学表现，并评估严重程度评分指数 (SSI)。进行了全面的神经系统、腹部和胸部检查。评估了超声肝脏和脾脏体积和 NFC。GD 基因型已完成。测量血清TIMP-1和VEGF。结果 与对照组相比，具有 GD 的 CA 具有显着更高的 TIMP-1 (P < 0.001) 和 VEGF (P < 0.001)。GD 型 3CA 的 TIMP-1 (P = 0.004) 和 VEGF (P = 0.035) 显着高于 1 型。 TIMP-1 与 VEGF (P < 0.001)、SSI (P < 0.001) 0.001) 和 NFC (P < 0.001)。发现 TIMP-1 与抽搐 (P = 0.002)、吞咽困难 (P = 0.008)、眼肌麻痹 (P = 0.038) 和发育迟缓 (P < 0.001) 之间存在显着的正相关关系。GD 儿童和青少年预测因子的多变量逻辑回归分析显示其与 TIMP-1 (P = 0.008) 和 NFC 变化 (P = 0.025) 最相关。结论 GD 中的巨噬细胞增殖调节局部炎症、微血管病和新血管生成。NFC 可用作 GD 微血管病变的无创指标。