Cardiac findings after enzyme replacement therapy for mucopolysaccharidosis type I
Cardiac findings after enzyme replacement therapy for mucopolysaccharidosis type I
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DOI：
10.1016/j.amjcard.2006.02.047
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发表时间：
2006-08-01
影响因子：
2.8
通讯作者：
Whitley, Chester B.
中科院分区：
文献类型：
--
作者：
Braunlin, Elizabeth A.;Berry, James M.;Whitley, Chester B.
粘多糖样沉积症I型是一种致死性常染色体隐性遗传病，由溶酶体α-L-艾杜糖醛酸酶缺乏和随后的糖胺聚糖全身蓄积引起。心肌病和瓣膜功能不全的发生是由于糖胺聚糖在心肌中积聚，扩张心脏瓣膜的海绵体，并在心外膜冠状动脉的肌内膜内增殖。在最严重的情况下，充血性心力衰竭和死亡发生在生命的前十年内。同种异体造血干细胞移植，用于严重形式的疾病，显著延长生存期，减少心室肥大，并保留心脏功能，但心脏瓣膜继续扩张和瓣膜功能不全的进展。对于造血干细胞移植的风险/获益比似乎不利的I型粘多糖样沉积症患者，已提出使用人重组α-L-艾杜糖醛酸酶的酶替代疗法作为替代疗法。研究者报告了一个小系列的5例I型粘多糖沉积症患儿的心脏表现，他们接受了长达7年的酶替代治疗。治疗期间未发生死亡。治疗前存在的左心室肥大在所有病例中均消退，心肌功能保持正常。相反，二尖瓣和主动脉瓣仍然增厚，在某些情况下，出现进行性增厚和反流。总之，长期酶替代疗法对心肌有一些明显的益处，但心脏瓣膜出现。无反应，对冠状血管的最终影响尚不清楚。(c)2006年爱思唯尔公司All rights reserved.
Mucopolysaccharidosis type I is a lethal autosomal recessive storage disease caused by a deficiency of lysosomal alpha-L-iduronidase and the consequent systemic accumulation of glycosaminoglycan. Cardiomyopathy and valvar insufficiency occur as glycosaminoglycan accumulates in the myocardium, expands the spongiosa of cardiac valves, and proliferates within the myointima of the epicardial coronary arteries. Congestive heart failure and death occur within the first decade of life in the most severe cases. Allogeneic hematopoietic stem cell transplantation, used in severe forms of the disease, markedly prolongs survival, alleviates ventricular hypertrophy, and preserves cardiac function, but cardiac valves continue to thicken and valvular insufficiency progresses. Enzyme replacement therapy with human recombinant alpha-L-iduronidase has been proposed as an alternativee therapy for, patients with mucopolysaccharidosis type I in whom the risk/benefit ratio of hematopoietic stem cell transplantation seems unfavorable. The investigators report the cardiac findings in a small series of 5 children with mucopolysaccharidosis type I who received enzyme replacement therapy for as long as 7 years. No deaths occurred during treatment. Left ventricular hypertrophy, which was present before therapy, resolved in all cases, and myocardial function remained normal. In contrast, the mitral and aortic valves remained thickened and, in some instances, developed progressive thickening and regurgitation. In conclusion, long-term enzyme replacement therapy has some clear benefits for the myocardium, but the cardiac valves appear. unresponsive, and the ultimate effect on the coronary vasculature is unknown. (c) 2006 Elsevier Inc. All rights reserved.