Ma X, Chen Z H, Zhang H T, He R X, Wang Q, Ding Y, Song J Q, Jin Y, Li M Q, Dong H, Zhang Y, Lu M, Lu X P, Cao H Q, Wang Y Q, Chen Y X, Zheng H, Yang Y L
Children's Medical Center, Peking University First Hospital, Beijing 102600, China.
Scientific Research and Innovation Center, Women and Children's Hospital, Xiamen University, Xiamen 361000, China.
Zhonghua Er Ke Za Zhi. 2024 Jun 2;62(6):520-525. doi: 10.3760/cma.j.cn112140-20240130-00083.
To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies. 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. Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). 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. 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.
探讨青少年型甲基丙二酸血症（MMA）的临床特征及转归，并探索预防策略。这是一项对青少年型MMA患者的表型、基因型和预后进行的回顾性病例分析。2002年1月至2023年6月在北京大学第一医院确诊的患者有55例，收集了症状、体征、实验室检查结果、基因变异及转归等数据。通过微信、电话或每3至6个月门诊随访。55例患者中，男性31例，女性24例。发病年龄为12岁（范围10 - 18岁）。他们在性征发育2至5期就诊，具有典型的第二性征。9例（16%）由感染诱发，5例（9%）由隐匿性运动诱发。从发病到诊断的时间为2个月至6年。45例（82%）以神经精神症状为主要表现，其次心血管症状12例（22%），肾脏损害7例（13%），眼部疾病12例（22%）。54例（98%）具有甲基丙二酸血症合并高同型半胱氨酸血症的生化特征，1例（2%）为单纯甲基丙二酸血症。54例获得基因诊断，在MMACHC基因中鉴定出20种变异，在MMUT基因中鉴定出2种变异。53例MMACHC基因突变患儿中，1例具有PRDX1和MMACHC的双基因变异，共105个等位基因。MMACHC中前5位常见变异为：c.482G>A 39个等位基因（37%），c.609G>A 17个等位基因（16%），c.658_660delAAG 11个等位基因（10%），c.80A>G 10个等位基因（10%），c.567dupT和c.394C>T均为4个等位基因（4%）。所有患者采用钴胺素、左卡尼汀、甜菜碱及对症治疗后均康复，54例（98%）恢复上学或工作。青少年型MMA患者可能由疲劳或感染诱发。由于症状不特异，诊断常延迟。代谢和基因检测对明确诊断至关重要。钴胺素、左卡尼汀和甜菜碱治疗可有效逆转青少年型MMA患者的预后。
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