Wang Qiong, Chen Yan, Li Jun, Li Baomin
Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China.
Transl Pediatr. 2025 Feb 28;14(2):367-372. doi: 10.21037/tp-24-462. Epub 2025 Feb 25.
Mitochondrial diseases represent a diverse group of disorders caused by defects in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA), leading to a wide range of clinical manifestations. These diseases can affect multiple organs, particularly the nervous system, and present with symptoms such as epilepsy, neurodevelopmental delays, and muscular disorders. Over 300 genetic mutations have been linked to these conditions, with clinical heterogeneity being a hallmark of mitochondrial diseases. Early diagnosis and management are crucial, especially in pediatric cases where the disease burden may evolve with age. The aim of this study is to explore the variability in clinical presentation and progression associated with specific genetic mutations, using the case of a rare mutation in the gene as an illustrative example, and to discuss the implications for clinical diagnosis.
This paper reports on a rare mutation, m.1630A>G, in the gene of a 3-year-old boy with epilepsy. In contrast to previously reported cases of the mitochondrial neurogastrointestinal encephalopathy (MNGIE)-like disease/the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) associated with the m.1630A>G mutation, this patient exhibited an earlier age of onset, simpler clinical manifestations, and lower heterogeneity levels in the blood.
This case offers significant insights into the intricate nature of mitochondrial diseases, especially in pediatric populations. It highlights the critical importance of regular physical examinations and vigilant monitoring for potential multi-system involvement, which are essential for early detection and timely symptomatic intervention to mitigate further damage. Furthermore, this case underscores the necessity to investigate factors influencing clinical penetrance, such as the interplay between mitochondrial and nuclear gene mutations, heterogeneity levels, and age-related accumulation of cellular damage, to better understand disease progression and optimize therapeutic strategies.
线粒体疾病是由线粒体DNA（mtDNA）或核DNA（nDNA）缺陷引起的一组多样的疾病，导致广泛的临床表现。这些疾病可影响多个器官，尤其是神经系统，表现为癫痫、神经发育迟缓及肌肉疾病等症状。超过300种基因突变与这些疾病相关，临床异质性是线粒体疾病的一个标志。早期诊断和管理至关重要，尤其是在儿科病例中，疾病负担可能随年龄增长而演变。本研究的目的是以某基因的一种罕见突变为例，探讨与特定基因突变相关的临床表现和进展的变异性，并讨论其对临床诊断的意义。
本文报告了一名3岁癫痫男孩某基因中一种罕见的m.1630A>G突变。与先前报道的与m.1630A>G突变相关的线粒体神经胃肠性脑病（MNGIE）样疾病/伴有乳酸性酸中毒和卒中样发作的线粒体脑肌病（MELAS）病例不同，该患者发病年龄更早，临床表现更简单，血液中的异质性水平更低。
该病例为线粒体疾病的复杂本质提供了重要见解，尤其是在儿科人群中。它强调了定期体检和对潜在多系统受累进行密切监测的至关重要性，这对于早期发现和及时进行对症干预以减轻进一步损害至关重要。此外，该病例强调了研究影响临床外显率的因素的必要性，如线粒体和核基因突变之间的相互作用、异质性水平以及与年龄相关的细胞损伤积累，以更好地了解疾病进展并优化治疗策略。
