Pan Pianpian, Zhou Na, Sun Yi, Chen Zhengrong, Han Jin, Zhou Wei
Nenoatal Intensive Care Unit, Guangzhou Wowen and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Heart Center, Guangzhou Wowen and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Front Pediatr. 2024 Sep 27;12:1410133. doi: 10.3389/fped.2024.1410133. eCollection 2024.
Coenzyme Q10 (CoQ10) plays an important role in the electron transport chain within the human mitochondrial respiratory chain. The manifestations of this deficiency exhibit a diverse range. This study investigates the clinical manifestations of primary coenzyme Q10 deficiency in neonates with the COQ4 mutation to improve the diagnosis of the disease and the prognosis through targeted treatment.
We report 4 patients with primary coenzyme Q10 deficiency by COQ4 variants in neonates. A comprehensive literature search and review for original articles and case reports with COQ4 mutation published from January 1989 to November 2023 was performed through Pubmed. We review clinical manifestations, diagnostic approaches, and treatment monitoring in these and 20 previously reported patients.
Within the cohort of four cases examined, three females and one male were identified from two distinct families. Specifically, case 1 and 2 consisted of monoamniotic twins. Cases 3 and 4 were siblings. A comprehensive review of 20 cases involving neonatal-onset COQ4 mutation was conducted. Half of the cases are Chinese. There was no statistically significant difference in the mortality between Chinese (9/12, 75%) and other regions (11/12, 91.7%) ( = 0.27). The survival time for the 24 cases was 60.0 ± 98.0 days (95% confidence interval CI: 0-252.0 days). The incidence of prenatal abnormalities in preterm infants was significantly higher than that in full-term infants (66.7% vs. 16.7%, = 0.02). Hyperlactatemia was one of the most common manifestations, accounting for 75% of cases (18/24). Twenty of the 24 cases were diagnosed by whole exome sequencing. Only 9 patients received exogenous coenzyme Q10 treatment, and all the 4 surviving patients received coenzyme Q10 supplementation.
The prognosis of COQ4 mutation in the neonatal period indicates a low survival rate and an poor prognosis. This may be due to the incomplete understanding of the mechanism of how COQ4 gene defects lead to coenzyme Q10 deficiency and why CoQ10 supplementation does not respond well to treatment. To improve the diagnostic rate, in addition to genetic testing, mitochondrial functional verification should be prioritized in southern China, where the incidence is relatively high. It will facilitate more in-depth mechanistic studies.
辅酶Q10（CoQ10）在人类线粒体呼吸链的电子传递链中起重要作用。这种缺乏症的表现多种多样。本研究调查了患有COQ4突变的新生儿原发性辅酶Q10缺乏症的临床表现，以通过针对性治疗改善疾病诊断和预后。
我们报告了4例新生儿因COQ4变异导致的原发性辅酶Q10缺乏症患者。通过Pubmed对1989年1月至2023年11月发表的有关COQ4突变的原始文章和病例报告进行了全面的文献检索和综述。我们回顾了这些患者以及之前报告的20例患者的临床表现、诊断方法和治疗监测情况。
在检查的4例病例中，从两个不同家庭中鉴定出3名女性和1名男性。具体而言，病例1和病例2是单羊膜囊双胞胎。病例3和病例4是兄弟姐妹。对20例涉及新生儿期COQ4突变的病例进行了全面综述。其中一半病例是中国人。中国患者（9/12，75%）和其他地区患者（11/12，91.7%）的死亡率无统计学显著差异（P = 0.27）。24例患者的生存时间为60.0±98.0天（95%置信区间CI：0 - 252.0天）。早产儿产前异常的发生率显著高于足月儿（66.7%对16.7%，P = 0.02）。高乳酸血症是最常见的表现之一，占病例的75%（18/24）。24例中有20例通过全外显子测序确诊。只有9例患者接受了外源性辅酶Q10治疗，4例存活患者均接受了辅酶Q10补充治疗。
新生儿期COQ4突变的预后表明生存率低且预后不良。这可能是由于对COQ4基因缺陷如何导致辅酶Q10缺乏以及为什么补充辅酶Q10治疗反应不佳的机制了解不全面。为提高诊断率，在中国南方发病率相对较高的地区，除基因检测外，应优先进行线粒体功能验证。这将有助于进行更深入的机制研究。
