Demaret Tanguy, Varma Sharat, Stephenne Xavier, Smets Françoise, Scheers Isabelle, Wanders Ronald, Van Maldergem Lionel, Reding Raymond, Sokal Etienne
Service de Gastro-Entérologie et Hépatologie Pédiatrique, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Academic Medical Center, Amsterdam, the Netherlands.
Pediatr Transplant. 2018 May;22(3):e13112. doi: 10.1111/petr.13112. Epub 2018 Feb 16.
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 (17 years post-LT) and short-term (9 months 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.
轻度泽尔韦格谱系障碍，也被称为婴儿型雷夫叙姆病，归因于PEX基因突变。其临床病程的特征是进行性听力和视力丧失以及神经发育倒退。目前支持性治疗被视为标准治疗方法，因为尚无治疗方法显示出临床益处。肝移植被证明可纠正循环中有毒代谢物的水平，这些代谢物部分导致慢性神经功能损害。在三名因轻度泽尔韦格谱系障碍接受肝移植的患者中，一名在肝移植后死亡，而另外两名在长期（肝移植后17年）和短期（肝移植后9个月）随访中均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、降植烷酸和哌可酸水平完全恢复正常。这与听力和视觉功能的稳定以及神经发育状况的改善相关，这使得年长的患者能够长期过上相对自主的生活方式。与未接受肝移植且神经学预后不良并伴有严重残疾的患病兄弟姐妹相比，其精神运动发育明显改善。我们推测，在轻度泽尔韦格谱系障碍出现严重感觉神经性缺陷之前进行肝移植能够实现部分代谢缓解并改善长期临床结局。
