Fabry disease.
Fabry disease.
复制标题
Fabry疾病。
DOI：
10.1186/1750-1172-5-30
复制
发表时间：
2010-11-22
影响因子：
3.7
通讯作者：
Germain DP
中科院分区：
文献类型：
--
作者：
Germain DP
法布里病（FD）是一种进行性、X连锁遗传性鞘糖脂代谢疾病，由于溶酶体α-半乳糖苷酶A活性缺乏或缺乏。FD是泛种族的，报告的10万分之一的年发病率可能低估了该疾病的真实患病率。典型受影响的半合子男性，没有残留的α-半乳糖苷酶A活性，可能会表现出所有特征性的神经系统（疼痛）、皮肤（血管角化瘤）、肾脏（蛋白尿、肾衰竭）、心血管（心肌病、心律失常）、耳蜗-前庭和脑血管（短暂性脑缺血发作、中风）疾病体征，而杂合子女性则表现出从非常轻微到严重的症状。溶酶体α-半乳糖苷酶A活性不足导致神经酰胺三己糖苷在溶酶体内进行性蓄积，据信可触发级联细胞事件。α-半乳糖苷酶A明显缺乏是诊断半合子男性的决定性方法。酶分析可以辅助检测杂合子，但由于随机X染色体失活，因此通常不确定，因此必须对女性进行分子检测（基因分型）。在儿童时期，必须排除其他可能的疼痛原因，如类风湿性关节炎和“生长痛”。在成年期，有时会考虑多发性硬化症。产前诊断可通过酶活性测定或绒毛膜绒毛或培养的羊膜细胞中的DNA检测进行，出于伦理原因，仅考虑男性胎儿。可以进行植入前诊断。非典型变异的存在和特定治疗的可用性使遗传咨询异常复杂。最近引入了一种疾病特异性治疗选择-使用重组人α-半乳糖苷酶A的酶替代疗法，目前仍在研究其长期结局。常规治疗包括使用止痛药缓解疼痛、肾保护（血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂）和抗血管病药物，而透析或肾移植可用于终末期肾衰竭患者。随着年龄的增长，对重要器官系统的渐进性损害会发展，在某些时候，器官可能开始功能衰竭。终末期肾病和危及生命的心血管或脑血管并发症限制了未经治疗的男性和女性的预期寿命，与一般人群相比，分别减少了20年和10年。虽然有越来越多的证据表明，长期酶治疗可以阻止疾病进展，但应强调连续治疗的重要性，开发口服治疗的可能性推动了对活性位点特异性分子伴侣的研究。
Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, whereas dialysis or renal transplantation are available for patients experiencing end-stage renal failure. With age, progressive damage to vital organ systems develops and at some point, organs may start to fail in functioning. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated males and females with reductions of 20 and 10 years, respectively, as compared to the general population. While there is increasing evidence that long-term enzyme therapy can halt disease progression, the importance of adjunctive therapies should be emphasized and the possibility of developing an oral therapy drives research forward into active site specific chaperones.
登录
查看更多内容
影响因子：
4.2
作者：
Baehner, F;Kampmann, C;Beck, M
通讯作者：
Beck, M
DOI：
10.1073/pnas.0712309105
发表时间：
2008-02-26
影响因子：
11.1
作者：
Aerts, Johannes M.;Groener, Johanna E.;Poorthuis, Ben J.
通讯作者：
Poorthuis, Ben J.
DOI：
10.1111/j.1365-2362.2004.01424.x
发表时间：
2004-12-01
影响因子：
5.5
作者：
Beck, M;Ricci, R;Mehta, A
通讯作者：
Mehta, A
影响因子：
5
作者：
Auray-Blais, Christiane;Ntwari, Aime;Gagnon, Rene
通讯作者：
Gagnon, Rene
影响因子：
4.2
作者：
Benjamin, E. R.;Flanagan, J. J.;Valenzano, K. J.
通讯作者：
Valenzano, K. J.