Living-donor liver transplantation for mild Zellweger spectrum disorder: Up to 17years follow-up
Living-donor liver transplantation for mild Zellweger spectrum disorder: Up to 17years follow-up
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DOI：
10.1111/petr.13112
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发表时间：
2018-05-01
影响因子：
1.3
通讯作者：
Sokal, Etienne
中科院分区：
文献类型：
--
作者：
Demaret, Tanguy;Varma, Sharat;Sokal, Etienne
轻度Zellweger谱系障碍，也被称为婴儿Refsum病，可归因于PEX基因突变。其临床过程的特点是进行性听力和视力下降，神经发育退化。支持性管理目前被认为是标准治疗，因为没有治疗显示出临床获益。LT被证明可以纠正循环中有毒代谢物的水平，这是慢性神经功能障碍的部分原因。在3例因轻度ZSD接受LT的患者中，1例在LT后死亡，而另外2例在长期（LT后17年）和短期（LT后9个月）随访中显示出显著的神经发育改善。我们记录了生化功能的持续改善，血浆植烷酸、降植烷酸和哌啶酸水平完全正常化。这与听力和视觉功能的稳定以及神经发育状态的改善有关，这使得老年患者能够长期保持相对自主的生活方式。与未接受LT并表现出严重残疾的不良神经学结局的受影响兄弟姐妹相比，精神障碍的获得得到了显著改善。我们推测在轻度ZSD患者出现严重感觉神经缺陷之前进行LT可以缓解部分代谢并改善长期临床结局。
Mild Zellweger spectrum disorder, also described as Infantile Refsum disease, is attributable to mutations in PEX genes. Its clinical course is characterized by progressive hearing and vision loss, and neurodevelopmental regression. Supportive management is currently considered the standard of care, as no treatment has shown clinical benefits. LT was shown to correct levels of circulating toxic metabolites, partly responsible for chronic neurological impairment. Of three patients having undergone LT for mild ZSD, one died after LT, while the other two displayed significant neurodevelopmental improvement on both the long-term (17years post-LT) and short-term (9months post-LT) follow-up. We documented a sustained improvement of biochemical functions, with a complete normalization of plasma phytanic, pristanic, and pipecolic acid levels. This was associated with stabilization of hearing and visual functions, and improved neurodevelopmental status, which has enabled the older patient to lead a relatively autonomous lifestyle on the long term. The psychomotor acquisitions have been markedly improved as compared to their affected siblings, who did not undergo LT and exhibited a poor neurological outcome with severe disabilities. We speculate that LT performed before the onset of severe sensorineural defects in mild ZSD enables partial metabolic remission and improved long-term clinical outcomes.