探讨儿童脑型X-连锁肾上腺脑白质营养不良(CCALD)患儿的临床表现及ABCD1基因突变类型。

选择2020年4月，四川大学华西第二医院收治的1例以癫痫发作为首发症状的CCALD患儿为研究对象。采用回顾性分析法，对本例患儿的临床病例资料，包括病史、临床表现及实验室检查、基因检测结果与诊治过程等进行研究。以"X-连锁肾上腺脑白质营养不良""儿童""ABCD1基因"及"X-linked adrenoleukodystrophy""child""ABCD1 gene"为中、英文关键词，对万方数据知识服务平台、中国知网等中文数据库，以及PubMed、外文医学信息资源检索平台(FMRS)、Embase等英文数据库，自2011年1月至2021年12月收录的CCALD患儿相关文献进行检索，并总结该病患儿临床表现及ABCD1基因突变特点。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求。

①本例患儿为男性，12岁7个月，因为"反复癫痫发作7年"，2020年4月首次于本院就诊。患儿首发症状为癫痫发作，并出现学习成绩及视力下降等。入院时头颅MRI结果显示，顶叶、颞叶脑白质区与侧脑室后角旁脑白质对称性异常信号影，累及双侧内囊后肢、双侧丘脑、胼胝体压部及大脑脚皮质脊髓束。基因检测结果显示，患儿ABCD1基因1号外显子c.589_590del半合子移码突变，p.L197Dfs*103氨基酸改变，该突变位点遗传自患儿母亲。对患儿采取左乙拉西坦30 mg/(kg·d)抗癫痫、胞磷胆碱营养神经、康复训练等治疗效果欠佳。截至2022年1月5日，患儿仍瘫痪卧床、胃管进食及不能正常交流，偶有肌阵挛样动作。②文献复习结果：关于ABCD1基因突变相关研究文献为23篇，涉及CCALD患儿为92例，包括75种不同类型ABCD1基因突变，以错义突变(62.7%，47/75)最为常见，其次是移码突变(25.3%，19/75)，突变最常发生于1号外显子(38.7%，29/75)。

CCALD患儿临床表现多样，典型首发症状以行为和认知障碍为主，但是部分患儿以严重神经系统功能异常首发。其头颅MRI典型表现为双侧顶叶、枕叶脑白质对称性病变；ABCD1基因突变以错义突变最为常见，多为1号外显子发生突变。

To explore clinical manifestations and mutation types of ABCD1 gene of children with childhood cerebral X-linked adrenoleukodystrophy (CCALD).

In April 2020, a CCALD boy with epilepsy episodes as first symptom who was treated in West China Second University Hospital, Sichuan University was selected as research subject. His clinical data, including medical history, clinical manifestations, laboratory examination and genetic test results, diagnosis and treatment process, etc. were analyzed by retrospectively analysis method. Literature related to research of children with CCALD was searched from Wanfang data knowledge service platform, China National Knowledge Infrastructure, and PubMed, Foreign Medical Literature Retrieval Service (FMRS) and Embase database by taking " X-linked adrenoleukodystrophy" " child" " ABCD1 gene" as the keywords both in Chinese and English. Literature retrieval time was set from January 2011 to December 2021. Clinical manifestations and ABCD1 gene mutation characteristics of CCALD in searched literature were summarized. This study was consistent with the requirements of World Medical Association Declaration of Helsinki revised in 2013.

①He was 12-year-7-month old, and first visited our hospital in April 2020 for " recurrent seizures for 7 years" . His initial symptom was epilepsy, decline in academic performance, impaired vision etc.. His cranial MRI results on admission showed a symmetrical abnormal signal shadow in alba of parietal lobe and temporal lobe and alba near cornu occipitale, involving posterior limbs of bilateral internal capsule, bilateral thalamus, splenium corporis callosi and cerebral peduncle-corticospinal tract. His genetic test showed that exon 1 of ABCD1 gene had c. 589_590del hemizygous frameshift mutation, resulting in amino acid change pL197Dfs*103, and this mutation was inherited from his mother. He was treated with levetiracetam 30 mg/(kg·d) for epilepsy, citicoline for nourishing nerves and rehabilitation training. His treatment effect was not good, and disease was getting worse. As of January 5, 2022, he was still paralyzed in bed, took food through gastric tube, could not communicate normally, and occasionally had myoclonic movements. ②Literature review results: a total of 23 pieces of literature related to CCALD, and 92 children, including 75 different types of ABCD1 gene mutations. The top 2 mutation types of ABCD1 gene were missense mutation (62.7%, 47/75) and frameshift mutation (25.3%, 19/75), and mutations most frequently occurred in exon 1 (38.7%, 29/75).

The clinical manifestations of CCALD are diverse. The initial symptoms include behavioral and cognitive disorders, but some children show severe neurological dysfunctions at the first onset. Typical features of cranial MRI are symmetrical lesions of alba in bilateral parietal and occipital lobes. Missense mutations are the most common mutations in ABCD1 gene, most of which occur in exon 1.