Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), U.O.C.di Medicina Interna con Stroke Care, Università degli Studi di Palermo, Piazza delle Cliniche n.2, 90127, Palermo, Italy.
Curr Gene Ther. 2018;18(2):96-106. doi: 10.2174/1566523218666180404161315.
Fabry's disease is a genetic disorder of X-linked inheritance caused by mutations in the alpha galactosidase A gene resulting in deficiency of this lysosomal enzyme. The progressive accumulation of glycosphingolipids, caused by the inadequate enzymatic activity, is responsible of organ dysfunction and thus of clinical manifestations. In the presence of a high clinical suspicion, a careful physical examination and specific laboratory tests are required, finally diagnosis of Fabry's disease is confirmed by the demonstration of absence or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females; in fact the performance of enzymatic activity assay alone in women is inconclusive. Measurement of the biomarkers Gb3 and Lyso Gb3 in biological specimens may facilitate diagnosis. Because of its multisystemic involvement Fabry's disease may present a large spectrum of clinical manifestations as acroparesthesias, hypohidrosis, angiokeratomas, signs and symptoms of cardiac, renal, cerebrovascular involvement (renal insufficiency, proteinuria, left ventricular hypertrophy, strokes). Enzyme replacement therapy with recombinant α- galactosidase A is actually the specific therapy for Fabry disease. Early beginning of this treatment has shown beneficial effects in particular in cardiac and renal disease, a less efficacy it has been reported in central nervous system involvement. ERT has shown to be associated to a significant reduction of Gb3 accumulation in several tissues, in particular heart and kidney; moreover it improves pain related quality of life. Next generation lysosomal storage disorder treatment is based on new strategic approaches as stem cell based therapy, pharmacological chaperones, viral gene therapy; concerning Fabry's disease, it has been recently addressed to great interest this last innovative method, that is to say viral gene therapy, for delivering recombination enzyme into main involved tissues; promising results have been reported in animal models. Great efforts have been made and are still required in this field in order to make available a more effective, safer, advantageous therapeutic strategy for patients with Fabry's disease.
法布里病是一种 X 连锁遗传的遗传性疾病，由α-半乳糖苷酶 A 基因突变引起，导致该溶酶体酶缺乏。由于酶活性不足，糖鞘脂的逐渐积累导致器官功能障碍，从而导致临床表现。在高度怀疑临床症状的情况下，需要进行仔细的体格检查和特定的实验室检查，最终通过在半合子男性中证明缺乏或减少α-半乳糖苷酶 A 酶活性和在杂合子女性中进行基因分型来确认法布里病的诊断；实际上，仅在女性中进行酶活性测定的结果是不确定的。在生物标本中测量 Gb3 和 Lyso Gb3 生物标志物可能有助于诊断。由于其多系统受累，法布里病可能表现出广泛的临床表现，如肢端感觉异常、少汗、血管角皮瘤、心脏、肾脏、脑血管受累的症状和体征（肾功能不全、蛋白尿、左心室肥厚、中风）。用重组α-半乳糖苷酶 A 进行酶替代治疗实际上是法布里病的特异性治疗。这种治疗的早期开始已显示出在心脏和肾脏疾病方面的有益效果，而在中枢神经系统受累方面则报道效果较差。ERT 已被证明与在许多组织中，特别是心脏和肾脏中 Gb3 积累的显著减少有关；此外，它还改善了与疼痛相关的生活质量。下一代溶酶体贮积症治疗基于新的战略方法，如基于干细胞的治疗、药理学伴侣、病毒基因治疗；关于法布里病，最近人们对这种创新方法，即病毒基因治疗，产生了极大的兴趣，即将重组酶递送到主要受累组织；在动物模型中已经报告了有希望的结果。在这个领域已经做出了巨大的努力，并且仍在继续努力，以便为法布里病患者提供更有效、更安全、更有利的治疗策略。
