LAUSR

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.