Vascular Endothelial Growth Factor (VEGF-a) in Fabry disease: Association with cutaneous and systemic manifestations with vascular involvement

IntroductionFabry disease is an X-linked inherited metabolic disorder characterized by the deficiency of lysosomal α-galactosidase A enzyme. This leads to the accumulation, into lysosomes through the body, of glycosphingolipids, mainly Gb3. Skin involvement and progressive multi-organ failure are usually observed. Endothelium is the preferential target of the Gb3 storage that determines endothelial dysfunction and vasculopathy leading to the clinical manifestations of the disease. The serum levels of Vascular Endothelial Growth Factor-A (VEGF-A), a specific endothelial cell mitogen, were analyzed in Fabry patients to explore a possible association to the clinical manifestations with vascular involvement.MethodsThirty-five patients with a biochemical and genetic diagnosis of Fabry disease, along with an age-gender-matched healthy control group, were enrolled. Serum samples were collected and analyzed by ELISA. The genetic mutations, the specific organ dysfunction, and the cardiovascular risk factors such as dyslipidaemia, diabetes, smoking habits and hypertension were evaluated in Fabry patients.ResultsThe mean serum level of VEGF-A in Fabry patients group was significantly higher than in the control group (P = 0.006). A statistical significant association, between VEGF-A levels and the skin manifestation including angiokeratomas, sweating abnormalities and Fabry Facies was found. An association was also found between high VEGF-A and specific GLA mutations, the male gender, the renal and neurological manifestations, the presence of eye vessels tortuosity, smoking habit and hypertension.ConclusionsWe detected increased VEGF-A levels in patients with Fabry disease compared to the controls, and we hypothesized that this could be a response to the vascular damage characterising this lysosomal disorder. However, further studies are necessary to clarify the role of VEGF-A in Fabry.

► Fabry is a lysosomal storage disorder leading to a progressive multi-organ failure. ► We analyzed serum VEGF-A in Fabry patients studying the association with clinical manifestations with vascular involvement. ► The VEGF-A levels were significantly higher in Fabry than in controls. ► Gene mutations, skin, eye, kidney, SNC involvement were associated the increased VEGF. ► VEGF production could be the response to the vascular damage described in Fabry.