Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Pediatric Surgery, Kyoto University Hospital, Kyoto, Japan.
Pediatr Transplant. 2024 Feb;28(1):e14659. doi: 10.1111/petr.14659. Epub 2023 Nov 27.
POLG is one of several nuclear genes associated with mitochondrial DNA maintenance defects and is a group of diseases caused by mitochondrial DNA deficiency that results in impaired adenosine triphosphate production and organ dysfunction. Myocerebrohepatopathy spectrum (MCHS) is the most severe and earliest presentation of POLG mutations, and liver transplantation (LT) for MCHS has never been reported.
The patient was a 3-month-old boy with acute liver failure and no neurological manifestations (e.g., seizures). We performed a living donor LT using a left lateral segment graft from his father. The postoperative course was uneventful. Subsequently, a homozygous POLG mutation (c.2890C>T, p. R964C) was identified by multigene analysis of neonatal/infantile intrahepatic cholestasis. Moreover, respiratory chain complex I, II, and III enzyme activities and the ratio of mtDNA to nuclear DNA in the liver were reduced. Therefore, we considered that these clinical manifestations and examination findings met the definition for MCHS. During meticulous follow-up, the patient had shown satisfactory physical growth and mental development until the time of writing this report.
We presumed that the absence of remarkable neurologic manifestations prior to LT in patients with MCHS is a good indication for LT and contributes to a better prognosis in the present case.
POLG 是与线粒体 DNA 维持缺陷相关的几个核基因之一，是一组由线粒体 DNA 缺乏引起的疾病，导致三磷酸腺苷生成受损和器官功能障碍。肌脑肝肾病谱（MCHS）是 POLG 突变最严重和最早的表现，而 MCHS 的肝移植（LT）从未有过报道。
患者为 3 月龄男性，急性肝功能衰竭，无神经系统表现（如癫痫发作）。我们使用来自其父亲的左外侧段移植物进行活体供者 LT。术后过程平稳。随后，通过新生儿/婴儿肝内胆汁淤积症的多基因分析，发现纯合 POLG 突变（c.2890C>T，p.R964C）。此外，肝内呼吸链复合物 I、II 和 III 酶活性以及线粒体 DNA 与核 DNA 的比值降低。因此，我们认为这些临床表现和检查结果符合 MCHS 的定义。在仔细的随访过程中，患者在报告撰写时表现出令人满意的体格生长和精神发育。
我们推测 MCHS 患者在 LT 前无明显神经表现是 LT 的良好指征，并有助于改善本例患者的预后。
