经典型同型半胱氨酸尿症13例临床及CBS基因分析  

Clinical characteristics and CBS gene analysis of 13 cases with classic homocystinuria

作　　者：李东晓 陈哲晖 金颖[2] 宋金青[2] 李梦秋 刘玉鹏[2] 李溪远[2] 陈永兴 张一宁[4] 吕国悦[4] 孙丽莹[5] 朱志军[5] 张尧[2] 杨艳玲[2] Li Dongxiao;Chen Zhehui;Jin Ying;Song Jinqing;Li Mengqiu;Liu Yupeng;Li Xiyuan;Chen Yongxing;Zhang Yining;Lyu Guoyue;Sun Liying;Zhu Zhijun;Zhang Yao;Yang Yanling(Henan Key Laboratory of Children′s Genetics and Metabolic Diseases,Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,China;Department of Pediatrics,Peking University First Hospital,Beijing 100034,China;Department of Endocrinology and Genetics and Metabolism,Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,China;Department of Pediatrics,the First Hospital of Jilin University,Changchun 130021,China;Department of General Surgery,Beijing Friendship Hospital of Capital Medical University,Beijing 100050,China)

机构地区：[1]郑州大学附属儿童医院河南省儿童遗传代谢性疾病重点实验室,郑州450018 [2]北京大学第一医院儿科,北京100034 [3]郑州大学附属儿童医院内分泌遗传代谢科,郑州450018 [4]吉林大学白求恩第一医院儿科,长春130021 [5]首都医科大学附属北京友谊医院普外科,北京100050

出　　处：《中华儿科杂志》2022年第6期533-538,共6页Chinese Journal of Pediatrics

基　　金：国家重点研发计划(2019YFC1005100);国家自然科学基金(82000850)。

摘　　要：目的分析经典型同型半胱氨酸尿症患儿的临床特点和CBS基因变异情况,探讨个体化治疗方法及预防。方法回顾性分析2013年11月至2021年6月就诊于郑州大学附属儿童医院及北京大学第一医院儿科的13例经典型同型半胱氨酸尿症患儿的一般情况、临床表现、实验室检查、头颅影像学、CBS基因变异特点、诊断及治疗等资料。结果13例患儿中男6例,女7例,确诊年龄为10日龄至14岁。3例为新生儿筛查检出,无症状时开始治疗,余10例于1~6岁发病,5~14岁时确诊,主要表现为马凡综合征样体型、晶状体脱位和(或)近视、发育落后、骨质疏松及心脑血管疾病。4例脑磁共振成像示不对称梗死灶,1例示髓鞘形成低下。13例患儿血清蛋氨酸、血清总同型半胱氨酸及尿液总同型半胱氨酸均增高,尿液甲基丙二酸正常,符合经典型同型半胱氨酸尿症。13例患儿CBS基因共检出18种变异,其中10种为新变异、8种为已知变异。仅1例为维生素B6部分反应型,12例为维生素B6无反应型,均以低蛋氨酸饮食及甜菜碱治疗为主,3例疗效不良患儿分别于3、8、8岁进行了肝移植治疗,术后1周内血液蛋氨酸及同型半胱氨酸恢复正常。1例患儿死亡。1例患儿母亲再孕时进行产前诊断,羊水细胞CBS基因存在与患儿相同的致病变异。结论经典型同型半胱氨酸尿症临床表现复杂多样,血氨基酸、血清及尿液总同型半胱氨酸和基因分析是诊断的关键。检出10种CBS基因新变异,扩展了CBS基因变异谱。肝移植为有效的治疗办法。产前诊断是防控经典型同型半胱氨酸尿症的重要措施。Objective To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria,and the strategies of individual treatment and prevention were explored.Methods The general information,clinical manifestations,laboratory tests,cranial images,CBS gene variants,diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children′s Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively.Results There were 13 patients diagnosed at the age of 10 days to 14 years,6 were male and 7 were female.There were 3 patients detected by newborn screening and received treatment at the asymptomatic stage.There were 10 patients clinically diagnosed at the age of 5 to 14 years.Their symptoms appeared at age of 1 to 6 years.The major clinical manifestations were marfanoid features,lens dislocation and(or)myopia,developmental delay,osteoporosis,and cardiovascular diseases.Brain magnetic resonance imaging showed asymmetric infarcts in 4 patients and hypomyelination in 1 case.Increased blood methionine,plasma total homocysteine and urinary total homocysteine with normal urinary methylmalonic acid were found in 13 patients.The biochemical features were consistent with classic homocystinuria.Totally 18 variants were identified in CBS gene of 13 patients,10 variants were novel and 8 were reported.only 1 patient was partially responsive to vitamin B6 treatment,while 12 cases were non-responsive.They were mainly treated with low methionine diet and betaine supplement.Three vitamin B6 non-responsive cases received liver transplantation at age of 3,8 and 8 years,respectively.Their blood methionine and total homocysteine returned to normal within a week after liver transplantation.One patient died.Prenatal diagnosis was performed for a fetus when the mother was pregnant again.Two pathogenic CBS gene variants were identified from the amniocytes as same as the proband.Con

关 键 词：肝移植 经典型同型半胱氨酸尿症 同型半胱氨酸 蛋氨酸 基因 CBS 

分 类 号：R725.8[医药卫生—儿科]