摘要目的:总结3-甲基戊烯二酸尿症Ⅷ型（3-methylglutaconic aciduria type Ⅷ，MGCA8）的临床表型及HTRA2基因变异特点。方法:回顾性分析珠海市妇幼保健院新生儿科收治的1例MGCA8患儿的临床资料。以“3-甲基戊烯二酸尿症”“3-甲基戊烯二酸尿症Ⅷ型”“HTRA2基因”为检索词，检索中国知网、中华医学期刊全文数据库、万方数据库、维普中文期刊数据库；以“3-methylglutaconic aciduria”“3-methylglutaconic aciduria type Ⅷ”“HTRA2 gene”为检索词检索医学文献数据库PubMed、Web of Science及Embase数据库，检索时间自建库至2024年7月，总结MGCA8患儿的临床表现和HTRA2基因变异特点。结果:本例患儿系足月顺产娩出，生后7 h渐出现反应欠佳伴喂养困难，生后18 h因“反应欠佳”入院，第1天有肢体抖动、肌张力减低，第2天开始肌张力增高。尿有机酸检测发现3-甲基戊烯二酸及3-甲基戊二酸升高，基因检测显示该患儿HTRA2基因发生c.213C>A（p.Cys71*）纯合变异，分别来自父母，为致病性变异。住院期间予低蛋白配方奶喂养、左卡尼汀口服及早期康复训练。2月龄时随访，患儿喂养困难，疑似癫痫，生长发育严重落后，营养不良；3月龄时因呼吸、循环衰竭死亡。文献检索共纳入13例MGCA8患儿，加上本例共14例，主要临床特征包括喂养困难（13/14）、肌张力异常（11/14）、呼吸困难或呼吸暂停（11/14）、震颤（8/14）、癫痫（7/14），部分患儿有眼球震颤、听力检测异常、颅脑磁共振成像异常，有2例患儿出现小头畸形，1例患儿有白内障。11例为基因检测确诊，3例为同家系中有MGCA8基因检测确诊者的相似症状，最终结局均为死亡。结论:对于新生儿期或婴儿期出现喂养困难、呼吸困难、肌张力异常、癫痫等表现的患儿，应考虑MGCA8的可能，HTRA2基因变异致MGCA8临床表型严重，存在早期致死性，尽早完善全外显子基因检测可明确诊断。

abstractsObjective:To study the clinical phenotype and HtrA Serine Peptidase 2 (HTRA2) gene mutation profiles of 3-methylglutaconic aciduria type Ⅷ (MGCA8).Methods:The clinical data of an infant with MGCA8 admitted to the neonatal department of our hospital were retrospectively analyzed. From inception to July 2024, multiple medical databases were searched using "3-methylpentene diaciduria" "3-methylpentene diaciduria type Ⅷ" and "HTRA2 gene" as key words. The clinical manifestations and HTRA2 mutation profiles of MGCA8 patients were summarized.Results:The infant was vaginally delivered at full term. Poor responsiveness and feeding difficulties gradually occurred 7 h after birth and he was admitted to the hospital due to "poor responsiveness" 18 h after birth. Limb tremor and decreased muscle tone were found on day1 and the muscle tone increased from day2. Urine organic acid examination showed elevated 3-methylpentaenoic acid and 3-methylglutaric acid. Genetic testing showed pathogenically homozygous variant of c.213C>A (p.Cys71*) in the HTRA2 gene, inherited from each parent. The treatment in hospital included low-protein formula feeding, oral levocarnitine and early rehabilitation. During follow-up, the infant had feeding difficulties, suspected epilepsy, severe growth retardation and malnutrition at 2 months of age and died due to respiratory and circulatory failure at 3 months. A total of 13 patients with MGCA8 were found in the literature (thus 14 cases including our patient). The main clinical features included feeding difficulties (13/14), abnormal muscle tone (11/14), dyspnea or apnea (11/14), tremor (8/14) and epilepsy (7/14). Some patients had nystagmus, hearing impairments and abnormal brain MRI findings. 2 cases had microcephaly and one had cataract. 11 cases were confirmed by genetic testing. 3 cases had similar symptoms with genetically confirmed MGCA8 patients in the same family. All patients died during follow-up.Conclusions:For infants with feeding difficulties, dyspnea, dystonia, epilepsy and other symptoms, MGCA8 should be considered. MGCA8 caused by HTRA2 gene mutation shows severe clinical phenotypes and early lethality. Early whole exome gene sequencing may confirm the diagnosis.