Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal disorder characterized by progressive gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, skeletal myopathy, ophthalmoparesis, and ptosis. MNGIE stems from deficient thymidine phosphorylase activity (TP) leading to toxic elevations of plasma thymidine. Hematopoietic stem cell transplant (HSCT) restores TP activity and halts disease progression but has high transplant-related morbidity and mortality. Liver transplant (LT) was reported to restore TP activity in two adult MNGIE patients. We report successful LT in four additional MNGIE patients, including a pediatric patient. Our patients were diagnosed between ages 14 months and 36 years with elevated thymidine levels and biallelic pathogenic variants in TYMP. Two patients presented with progressive gastrointestinal dysmotility, and three demonstrated progressive peripheral neuropathy with two suffering limitations in ambulation. Two patients, including the child, had liver dysfunction and cirrhosis. Following LT, thymidine levels nearly normalized in all four patients and remained low for the duration of follow-up. Disease symptoms stabilized in all patients, with some manifesting improvements, including intestinal function. No patient died, and LT appeared to have a more favorable safety profile than HSCT, especially when liver disease is present. Follow-up studies will need to document the long-term impact of this new approach on disease outcome. Take Home Message: Liver transplantation is effective in stabilizing symptoms and nearly normalizing thymidine levels in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and may have an improved safety profile over hematopoietic stem cell transplant.

中文翻译：

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线粒体神经胃肠脑肌病（MNGIE）肝移植成功。

线粒体神经胃肠脑病 (MNGIE) 是一种致命的疾病，其特征是进行性胃肠动力障碍、周围神经病、白质脑病、骨骼肌病、眼肌麻痹和上睑下垂。MNGIE 源于胸苷磷酸化酶活性 (TP) 缺陷导致血浆胸苷毒性升高。造血干细胞移植 (HSCT) 可恢复 TP 活性并阻止疾病进展，但移植相关的发病率和死亡率较高。据报道，肝移植 (LT) 可恢复两名成年 MNGIE 患者的 TP 活性。我们报告了另外四名 MNGIE 患者的成功 LT，其中包括一名儿科患者。我们的患者在 14 个月至 36 岁之间被诊断出胸苷水平升高和 TYMP 中的双等位基因致病变异。两名患者表现为进行性胃肠道运动障碍，三名患者表现为进行性周围神经病变，两名患者行走受限。包括孩子在内的两名患者患有肝功能障碍和肝硬化。LT 后，所有 4 名患者的胸苷水平几乎恢复正常，并在随访期间保持低水平。所有患者的疾病症状都稳定了，有一些明显的改善，包括肠道功能。没有患者死亡，并且 LT 似乎比 HSCT 具有更有利的安全性，尤其是当存在肝病时。后续研究需要记录这种新方法对疾病结果的长期影响。带回家留言：