Balwani Manisha, Burrow Thomas Andrew, Charrow Joel, Goker-Alpan Ozlem, Kaplan Paige, Kishnani Priya S, Mistry Pramod, Ruskin Jeremy, Weinreb Neal
Department of Genetics and Genomic Sciences, One Gustave L. Levy Place, Box 1497, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cincinnati Children's Hospital Medical Center, Division of Human Genetics, 3333 Burnet Avenue, MLC 4006, Cincinnati, OH 45229, USA.
Mol Genet Metab. 2016 Feb;117(2):95-103. doi: 10.1016/j.ymgme.2015.09.002. Epub 2015 Sep 7.
In Gaucher disease, deficient activity of acid β-glucosidase results in accumulation of its substrates, glucosylceramide and glucosylsphingosine, within the lysosomes of cells primarily in the spleen, liver, bone marrow, and occasionally the lung. The multisystem disease is predominantly characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. Enzyme replacement therapy with recombinant human acid β-glucosidase has been the first-line therapy for Gaucher disease type 1 for more than two decades. Eliglustat, a novel oral substrate reduction therapy, was recently approved in the United States and the European Union as a first-line treatment for adults with Gaucher disease type 1. Eliglustat inhibits glucosylceramide synthase, thereby decreasing production of the substrate glucosylceramide and reducing its accumulation. Although existing recommendations for the care of patients with Gaucher disease remain in effect, unique characteristics of eliglustat require additional investigation and monitoring. A panel of physicians with expertise in Gaucher disease and experience with eliglustat in the clinical trials provide guidance regarding the use of eliglustat, including considerations before starting therapy and monitoring of patients on eliglustat therapy.
在戈谢病中,酸性β-葡萄糖苷酶活性不足导致其底物葡萄糖神经酰胺和葡萄糖鞘氨醇在主要位于脾脏、肝脏、骨髓,偶尔也在肺部的细胞溶酶体内蓄积。这种多系统疾病主要表现为肝脾肿大、贫血、血小板减少和骨骼疾病。二十多年来,重组人酸性β-葡萄糖苷酶的酶替代疗法一直是1型戈谢病的一线治疗方法。艾考糊精是一种新型口服底物减少疗法,最近在美国和欧盟被批准作为1型戈谢病成人患者的一线治疗药物。艾考糊精抑制葡萄糖神经酰胺合酶,从而减少底物葡萄糖神经酰胺的产生并减少其蓄积。尽管现有的戈谢病患者护理建议仍然有效,但艾考糊精的独特特性需要进一步研究和监测。一组在戈谢病方面具有专业知识且在临床试验中使用过艾考糊精的医生就艾考糊精的使用提供了指导,包括开始治疗前的注意事项以及对接受艾考糊精治疗患者的监测。