新生儿期起病的1例Leigh综合征并文献复习

A Rare Case of Neonatal-Onset Leigh Syndrome with a Comprehensive Literature Review

摘要: 目的：报告1例线粒体ND3基因上m.T10158C位点突变导致1例临床罕见、以重度肺动脉高压为突出表现的Leigh综合征的临床特点，丰富m.T10158C突变的临床表型谱。方法：回顾性分析1例经过基因检测确诊的新生儿期发病的Leigh综合征的临床资料，复习相关文献并探讨由线粒体ND3基因突变引起的相关疾病表型及特点。结果：该病例的先证者自新生儿期起病，主要表现为持续的重度肺动脉高压、喂养困难、高血糖、四肢肌张力低下、反应差、面色苍白等多系统退行性表现。头颅MRI弥散像示脑干、双侧基底节–放射冠区、胼胝体压部、额叶见片状高信号影，脑内多发异常信号，血清乳酸升高。以外周血标本行线粒体基因检测提示chrM-10158T>C基因突变，结合患儿的临床特点及基因分析，该患儿确诊疾病表型为Leigh Disease，后因治疗难度大、病情恶化在1月内死亡。结论：此次先证者发病极早，以持续重度肺动脉高压为核心表现，经治后仍难以纠正，病情不断恶化后死亡，为目前相关报道中，该突变所致疾病于新生儿期死亡的严重极端表型，是发病年龄最小的案例之一，警示医师的早期识别。复习以往文献，该位点基因突变表现出从新生儿期的Leigh综合征到成人MELAS综合征的巨大临床异质性，为探讨线粒体疾病的基因型–表型关系提供了有价值的案例资料。

Abstract: Objective: To present a case report of Leigh syndrome caused by the m.T10158C mutation in the mitochondrial ND3 gene, which manifested with a clinically rare and predominant presentation of severe pulmonary arterial hypertension. This report aims to enrich the clinical phenotypic spectrum associated with the m.T10158C mutation. Methods: A retrospective analysis was conducted on the clinical data of a neonate diagnosed with Leigh syndrome through genetic testing. Relevant literature was reviewed to investigate the disease phenotypes and features associated with mitochondrial ND3 gene mutations. Results: The proband presented with multi-system degenerative manifestations from the neonatal period, including persistent severe pulmonary hypertension, feeding difficulties, hyperglycemia, limb hypotonia, poor responsiveness, and pallor. Brain diffusion-weighted MRI revealed patchy high-signal intensities in the brainstem, bilateral basal ganglia and corona radiata, splenium of the corpus callosum, and frontal lobe, indicating multiple intracranial abnormalities. Serum lactate levels were elevated. Genetic testing of a peripheral blood sample identified an m.10158T>C mutation. Based on the clinical features and genetic analysis, the patient was diagnosed with Leigh syndrome. Unfortunately, the patient succumbed to the disease within one month due to rapid deterioration and treatment challenges. Conclusion: The proband in this case exhibited an extremely early onset, with refractory severe pulmonary arterial hypertension as the core manifestation. Despite treatment, the hypertension remained uncorrected, and the patient’s condition progressively deteriorated, resulting in death. This represents one of the most severe and extreme phenotypes reported for this mutation—neonatal fatality—and is among the youngest cases in terms of age of onset, highlighting the critical need for early recognition by clinicians. A review of the existing literature reveals that mutations at this site demonstrate considerable clinical heterogeneity, ranging from Leigh syndrome in the neonatal period to MELAS syndrome in adults. This case provides valuable material for exploring genotype-phenotype correlations in mitochondrial disorders.