Objective: To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies. Methods: This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months. Results: Among the 55 patients, 31 were males and 24 were females. The median age of onset was 12 years old (range 10-18 yearsold). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work. Conclusions: Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.
目的： 探讨青春期起病的迟发型甲基丙二酸血症患儿的临床特点、诊断治疗及随访。 方法： 回顾性病例分析。选择2002年1月至2023年6月于北京大学第一医院确诊的青春期起病的55例甲基丙二酸血症患儿为研究对象，收集患儿症状、体征、检验结果、基因变异等临床资料，每3或6个月通过微信、电话或门诊进行随访（截至2023年12月），对患儿的临床表型、基因型及转归进行总结。 结果： 55例患儿中男31例、女24例，于10~18岁发病，中位发病年龄为12岁，第二性征发育均正常，就诊时Tanner 2~5期。9例（16%）在感染后起病，5例（9%）在剧烈运动后起病，从发病到确诊的时间历经2个月至6年。45例（82%）主要表现为神经精神疾病，12例（22%）出现心血管损伤，7例（13%）出现肾脏损伤，12例（22%）合并眼病。54例（98%）患甲基丙二酸血症合并同型半胱氨酸血症，1例患单纯型甲基丙二酸血症（2%）。54例获得了基因诊断，发现20种MMACHC基因变异和2种MMUT基因变异。53例MMACHC基因变异患儿中，1例为PRDX1和MMACHC双基因变异，共105个等位基因变异，前5位高频度变异为39个（37%）c.482G>A、17个（16%）c.609G>A、11个（10%）c.658_660delAAG、10个（10%）c.80A>G、4个（4%）c.567dupT和4个（4%）c.394C>T。所有患儿经过钴胺素、左卡尼汀、甜菜碱和对症治疗后逐渐康复，54例（98%）恢复正常就学和工作。 结论： 青春期起病的甲基丙二酸血症患儿多为合并型，发病隐匿，部分因疲劳或感染诱发疾病，临床识别困难，容易被延误诊断。生化代谢和基因检测是获得正确诊断的关键，通过钴胺素、左卡尼汀和甜菜碱治疗可以显著改善病情。.