儿童杜氏肌营养不良及携带者诊治的回顾性分析-东南大学学报医学版

儿童杜氏肌营养不良及携带者诊治的回顾性分析

单位：1. 南京医科大学第一附属医院儿科, 江苏南京 210029;
2. 南京医科大学第一附属医院生殖遗传检测中心, 江苏南京 210029

分类号：R726.85

出版年·卷·期（页码）：2023·42·第一期（1-8）

摘要：

目的：探讨杜氏肌营养不良（Duchenne muscular dystrophy，DMD）患儿及携带者的临床特点、基因突变类型、治疗等，为早期诊断该病及进一步有效治疗进行总结。方法：回顾性分析2010年1月至2022年6月在本院经基因检测确诊的17例男性DMD患儿及1例女性携带者的临床资料。结果：17例DMD患儿平均诊断年龄5.9岁（1个月~12岁），1例女性携带者诊断年龄6岁。血清酶谱示谷丙转氨酶、谷草转氨酶、乳酸脱氢酶、α-羟丁酸脱氢酶、肌酸激酶同工酶、肌酸激酶（creatine kinase，CK）水平均升高，以CK水平升高最为显著，为正常值的3.7~102倍（629~17 456 U·L^-1）。18例患儿中83.3%（15/18）存在缺失突变，其中45~55外显子缺失占41%；11.1%（2/18）为重复突变；5.5%（1/18）为内含子剪切突变。13例进行母亲基因检测验证，3例母亲未见DMD基因突变。1例患儿左上肢肱二头肌肌肉活检显示，病理改变为肌纤维萎缩、新生发育肌纤维、dystrophin蛋白局灶区肌膜表达减弱或缺失。4例肌电图检查均提示肌源性损害，DMD患儿三维运动步态分析提示双下肢部分肌群募集不良，以股直肌、股二头肌为主。1例DMD患儿行脐血间充质干细胞输注，5 d后CK下降77.0%。结论：对血清肌酶异常、运动功能异常儿童应高度警惕DMD，尽早行基因检测确诊，家族女性携带者须进行遗传咨询和产前诊断。

Objective: To retrospectively analyze the clinical characteristic, gene mutation and treatment of 18 children with Duchenne muscular dystrophy(DMD) and provide a basic knowledgel for early diagnosis and effective treatment. Methods: A retrospective analysis was performed on the clinical features of 17 DMD boys and one carrier girl who were admitted to the First Affliated Hospital of Nanjing Medical University from January 2010 to June 2022. Results: The mean age of diagnosis of DMD was 5.9 years(1 month to 12 years),the carrier was 6 years old. Laboratory results showed that alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH), α-hydroxybutyrate dehydrogenase(HBDH), creatine kinase isoenzyme(CKMB), creatine kinase(CK) were remarkably increased,especially CK was 3.7-102 times the normal level. Gene was tested in all 18 patients, including 83.3%(15/18) deletion mutations, among which exon 45-55 deletion accounted for 41%,11.1%(2/18) duplicate mutations,and 5.5%(1/18) intron splicing mutations. 13 cases were verified by maternal genetic testing, and 3 cases had no DMD gene mutation. One patient underwent muscle biopsy of the biceps brachialis of the left upper limb, and the pathological changes were muscle fiber atrophy, newly developed muscle fiber, and reduced or absent expression of dystrophin protein of focal myofilament. Four electromyography tests suggested myogenic damage. Three dimensional gait analysis of DMD child suggested poor recruitment of some muscle groups in both lower limbs, mainly rectus femoris and biceps femoris. CK in one case declined by 77.0% 5 days after umbilical cord blood mesenchymal stem cell therapy. Conclusion: For children with abnormal serum muscle enzymes and motor function, DMD should be diagnosed by genetic testing as early as possible with vigilance. Genetic counseling and prenatal diagnosis are needed in the family with female carriers.

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