Breunig Frank, Knoll Anita, Wanner Christoph
Department of Medicine, Division of Nephrology, University of Würzburg, Würzburg, Germany.
Curr Opin Nephrol Hypertens. 2003 Sep;12(5):491-5. doi: 10.1097/00041552-200309000-00002.
Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A. The lack of enzyme activity results in an intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide, in various tissues. Significant morbidity is caused by progressive effects on the vascular endothelium, heart, brain and kidney leading to end-stage renal disease. In this review we would like to give a current overview on recent advances in therapy and an outlook on future aspects in the management of Fabry disease.
Besides symptomatic management, enzyme replacement therapy with recombinant alpha-galactosidase A is the only specific treatment currently available. Clinical trials using recombinant alpha-galactosidase A showed safety and efficacy in reversing substrate storage in different tissues. Short-term response on clinical manifestations such as impaired kidney function demonstrates a clear potential to improve and stabilize symptoms of the disease. In patients with residual enzyme activity enzyme enhancement therapy with pharmacological chaperones seems to be an attractive approach. Enzyme replacement therapy mediated by gene transfer may become a promising alternative treatment strategy in the future.
Remarkable advances in the treatment of patients with Fabry disease have been made with the introduction of enzyme replacement therapy in clinical use. Although lysosomal globotriaosylceramide deposits are cleared very effectively, longer term experience on clinical outcome in patients with severe vital organ involvement is still limited.
法布里病是一种X连锁溶酶体贮积症，由α-半乳糖苷酶A缺乏引起。酶活性缺乏导致糖鞘脂（主要是Globotriaosylceramide）在各种组织细胞内蓄积。对血管内皮、心脏、大脑和肾脏的渐进性影响会导致严重发病，最终发展为终末期肾病。在本综述中，我们将概述法布里病治疗的最新进展，并展望其未来治疗的各个方面。
除了对症治疗外，重组α-半乳糖苷酶A的酶替代疗法是目前唯一可用的特异性治疗方法。使用重组α-半乳糖苷酶A的临床试验表明，该疗法在逆转不同组织中的底物蓄积方面具有安全性和有效性。对肾功能受损等临床表现的短期反应表明，该疗法具有改善和稳定疾病症状的明显潜力。对于具有残余酶活性的患者，使用药物伴侣进行酶增强疗法似乎是一种有吸引力的方法。基因转移介导的酶替代疗法未来可能成为一种有前景的替代治疗策略。
随着酶替代疗法在临床中的应用，法布里病患者的治疗取得了显著进展。尽管溶酶体Globotriaosylceramide沉积物能被非常有效地清除，但对于严重重要器官受累患者的长期临床结局经验仍然有限。
