一例MT-TL1 m.3243 A>G相关线粒体病患者在多系统表现出现前接受重组人生长激素暴露：十年病例报告

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中文摘要

背景： 线粒体脑肌病（ME）临床表现异质性强，常被误诊为单器官疾病。重组人生长激素（rhGH）常用于治疗儿童矮身材，但其在未确诊ME患者中的安全性仍不确定，理论上担心其可能加重多系统疾病进展。
病例介绍： 我们报告一例经基因确诊的ME患者，为24岁男性，随访十余年。患者于2015年14岁时因儿童期矮身材接受rhGH治疗，之后出现一系列多系统表现：2017年出现上睑下垂和认知下降，2018年发生类似中暑的急性代谢危象。此后数年间，他先后被诊断出多种疾病，包括慢性鼻窦炎、感音神经性听力损失、糖尿病（HbA1c 7.25%）、伴肌钙蛋白升高的心肌肥厚（0.016 ng/L）以及明显的小脑萎缩。实验室检查持续显示高乳酸血症（3.72 mmol/L），神经心理测试提示轻至中度认知障碍（MMSE 21，MoCA 13）。
结论： 本病例中观察到的时间顺序提示rhGH暴露与随后多系统疾病表现之间可能存在时间关联。然而，这一单例观察不能确立因果关系；所观察到的时间线可能部分反映了MELAS谱系疾病的自然史，该病常在青春期和成年早期表现为多系统受累。尽管如此，本报告强调在开始rhGH治疗前对潜在线粒体疾病保持临床警惕并进行全面评估的重要性，尤其是对伴有细微神经系统症状的矮身材儿童。

英文摘要

BACKGROUND: Mitochondrial encephalomyopathy (ME) is clinically heterogeneous and frequently misdiagnosed as a single-organ disease. While recombinant human growth hormone (rhGH) is commonly used to treat short stature in children, its safety in patients with undiagnosed ME remains uncertain, with theoretical concerns that it may exacerbate multisystem disease progression.
CASE PRESENTATION: We described a genetically confirmed case of ME in a 24-year-old male patient over a decade. After receiving rhGH therapy at age 14 in 2015 for childhood short stature, he developed a cascade of multisystem manifestations: ptosis and cognitive decline emerged in 2017, followed by an acute metabolic crisis resembling heatstroke in 2018. Over the following years, he was diagnosed with a succession of conditions, including chronic sinusitis, sensorineural hearing loss, diabetes (HbA1c 7.25%), myocardial hypertrophy with elevated troponin (0.016 ng/L), and marked cerebellar atrophy. Laboratory studies consistently showed hyperlactatemia (3.72 mmol/L), and neuropsychological testing indicated mild to moderate cognitive impairment (MMSE 21, MoCA 13).
CONCLUSIONS: The chronological correlation observed in this case suggested a possible temporal association between rhGH exposure and subsequent multisystem disease expression. However, this single case observation does not establish causality; the observed timeline may, in part, reflect the natural history of MELAS-spectrum disease, which often manifests multisystem involvement during adolescence and early adulthood. Nonetheless, this report highlights the importance of clinical vigilance and thorough evaluation for underlying mitochondrial disorders prior to initiating rhGH treatment, especially in children with short stature and subtle neurological symptoms.