摘要
目的 单纯型甲基丙二酸血症、丙酸血症和异戊酸血症是经典的有机酸血症,严重患者肝脏N-乙酰谷氨酸合成不足,尿素循环受阻,导致高氨血症等代谢危象,急性期快速降氨、纠正代谢性酸中毒是防治代谢性脑病的关键。本研究主要目的是分析卡谷氨酸在防治单纯型甲基丙二酸血症、丙酸血症和异戊酸血症所致高氨血症的有效性和安全性。方法 研究对象为来自全国七家医院的22例合并高氨血症的单纯型甲基丙二酸血症、丙酸血症和异戊酸血症患者,分为急性.代谢危象组和稳定期使用组,口服卡谷氨酸,监测血氨.及病情变化,观察卡谷氨酸的安全性和有效性。结果 22例患者中男14例,女8例,中位年龄为185个月,中位体重为9kg,既往平均每年代谢危象发作.31次,其中14例患MMUT基因缺陷所致单纯型甲基.丙二酸血症,7例患丙酸血症,1例患异戊酸血症。14例为急性代谢危象组,平均每年代谢危象发作3l5次,8例为稳定期使用.组,平均每年代谢危象发作26次l。急性代谢危象组卡.谷氨酸平均治疗剂量为85稳定期使用组卡谷氨酸平均治疗剂量为14L,平均随访时间为55天。服用卡谷氨酸后,所有患者食欲均改善,体重增加,未发生不良事件。结论 卡谷氨酸对有机酸血症代谢危象合并高氨血症及稳定期长期治疗有良好的有效性和安全性。
Objective Isolated methylmalonic acidemia,propionic acidemia and isovaleric acidemia are classic organic acidemias.In severe cases,urea cycle defect occurs due to insufficient synthesis of liver N-acetylglutamate resulting in hyperammonemia and metabolic crisis.Rapid reduction of ammonia and correction of metabolic acidosis are keys in the treatment of metabolic encephalopathy.The main purpose of this study was to investigate the effectiveness and safety of carglumic acid in the prevention and treatment of hyperammonemia caused by isolated methylmalonic acidemia,propionic acidemia and isovaleric acidemia.MethodsThe study included 22 patients of isolated methylmalonic acidemia,propionic acidemia and isovaleric acidemia with hyperammonemia from seven hospitals of China.They were divided into acute metabolic crisis group and long-term observation group.All patients received oral carglumic acid.Their blood ammonia levels,the safety and efficacy of carglumic acid were monitored.ResultsAmong 22 patients,14 were male and 8 were female,with a median age of 18.5 months and a median weight of 9 kg.The average annual frequency of metabolic crisis was 3.1 times.14 patients had isolated methylmalonic acidemia caused by MMUT gene defects.Seven patients had propionic acidemia.One patient had isovaleric acidemia.The average annual frequency of decompensation attack of 14 patients in the acute metabolic crisis group were 3.5 times.The average annual acute metabolic decompensations of 8 cases in the long-term observation group were 2.6 times.The average doses of carglumic acid in the acute metabolic crisis group was 85.9 mg/(kg·d).Their average blood ammonia level was 175.3μmol/L before treatment.At an average period of 28.9 hours after treatment,their blood ammonia level decreased to 45.8μmol/L.Their average treatment duration was 3.3 days.The average doses of carglumic acid in the long-term management group was 14.4 mg/(kg·d).Before treatment,their average blood ammonia level was 69.8μmol/L.After treatment,the blood ammonia level decreased to 51.5μmol/L at average of 50.4 hours.Their average follow-up period was 55 days.All patients showed improved appetite and increased body weight,with no adverse events reported.Conclusions Carglumic acid exhibited optimal effectiveness and safety in the management of hyperammonemia of the patients with organic acidemias during the stage of metabolic crisis and stable period.
作者
李东晓
董慧
商晓红
陈永兴
卫海燕
王彩君
刘大鹏
康文清
邱文娟
库尔班江·阿布都西库尔
陈晓红
刘丽
张尧
陈昊
王茜
杨艳玲
LI Dong-xiao;DONG Hui;SHANG Xiao-hong;CHEN Yong-xing;WEI Hai-yan;WANG Cai-jun;LIU Da-peng;KANG Wen-qing;QIU Wen-juan;ABUDUXIKUER Kuerbanjiang;CHEN Xiao-hong;LIU Li;ZHANG Yao;CHEN Hao;WANG Qian;YANG Yan-ling(Henan Children’s Neurodevelopment Engineering Research Center,Children’s Hospital Affiliated to Zhengzhou University,Henan Children’s Hospital Zhengzhou Children’s Hospital,Zhengzhou 450018,Henan Province,China;Children's Medical Center,Peking University First Hospital,Beijing 102600,China;Department of Pediatric Endocrinology,Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,Shandong Province,China;Department of Endocrinology,Genetics and Metabolism,Children’s Hospital Affiliated to Zhengzhou University,Henan Children’s Hospital Zhengzhou Children’s Hospital,Zhengzhou 450018,Henan Province,China;Neonatal Disease Diagnosis and Treatment Center,Children’s Hospital Affiliated to Zhengzhou University,Henan Children’s Hospital Zhengzhou Children's Hospital,Zhengzhou 450018,Henan Province,China;Department of Pediatric Endocrinology and Genetic Metabolism,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China;Department of Hepatology,Children’s Hospital Affiliated to Fudan University,Shanghai 201102,China;Department of Metabolism and Endocrinology,Wuhan Children’s Hospital,Wuhan 430015,Hubei Province,China;Department of Genetics and Endocrinology,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou 510623,Guangdong Province,China;Huazhong University of Science and Technology Base of National Institute of Healthcare Security,Wuhan 430030,Hubei Province,China)
出处
《罕少疾病杂志》
2024年第6期1-3,共3页
Journal of Rare and Uncommon Diseases
基金
国家重点研发计划(2021YFC2700903,2022YFC2703401)
国家自然科学基金(82000850)。
关键词
有机酸血症
甲基丙二酸血症
丙酸血症
异戊酸血症
高氨血症
卡谷氨酸
Organic Acidemia
Methylmalonic Acidemia
Propionic Acidemia
Isovaleric Acidemia
Hyperammonia
Carglumic Acid
