目的 总结GAMT基因变异所致肌酸缺乏综合征(creatine deficiency syndrome, CDS)的临床表现及遗传学特点。 方法 回顾性分析2020年12月—2024年12月中南大学湘雅医院儿童医学中心诊治的2例GAMT缺乏型CDS患儿的临床和遗传学资料。 结果 2例患儿均为婴幼儿期起病,GAMT基因均存在复合杂合变异,病例1表现为癫痫发作和智力障碍,病例2存在智力障碍及注意力缺陷多动障碍;2例患儿头颅磁共振波谱提示肌酸峰减低。肌酸治疗后病例1癫痫发作控制,2例患儿仍存在智力障碍及行为问题。截至2024年12月,国内共报道21例患者(包括本研究),国外报道115例。所有患者均有发育迟缓或智力障碍,66.9%(91/136)患者有癫痫发作,33.8%(46/136)患者存在运动障碍,36.8%(50/136)患者有行为问题,75.0%(102/136)患者接受肌酸治疗,癫痫发作及运动障碍可明显改善,认知改善不明显。 结论 GAMT缺乏型CDS罕见且临床表现不特异,及时诊断有助于针对性治疗,可部分改善预后。
Abstract
Objective To summarize the clinical manifestations and genetic characteristics of creatine deficiency syndrome (CDS) caused by GAMT gene mutations. Methods A retrospective analysis was conducted on the clinical and genetic data of two children diagnosed with GAMT deficiency-type CDS at the Children's Medical Center of Xiangya Hospital, Central South University, from December 2020 to December 2024. Results The two patients presented with symptoms in infancy, and both had compound heterozygous mutations in the GAMT gene. Case 1 exhibited seizures and intellectual disability, while Case 2 had intellectual disability and attention-deficit hyperactivity disorder. Magnetic resonance spectroscopy of cranial MRI in both patients indicated reduced creatine peaks. After creatine treatment, seizures in Case 1 were controlled, but both patients continued to experience intellectual disabilities and behavioral issues. As of December 2024, a total of 21 cases have been reported in China (including this study), and 115 cases have been reported abroad. All patients exhibited developmental delay or intellectual disabilities, with 66.9% (91/136) experiencing seizures, 33.8% (46/136) presenting with motor disorders, and 36.8% (50/136) having behavioral problems. Seventy-five percent (102/136) of patients received creatine treatment, leading to significant improvements in seizures and motor disorders, although cognitive improvement was not substantial. Conclusions GAMT deficiency-type CDS is rare and presents with nonspecific clinical features. Timely diagnosis facilitates targeted treatment, which can partially improve prognosis.
关键词
肌酸缺乏综合征 /
GAMT基因 /
智力障碍 /
癫痫 /
基因变异 /
儿童
Key words
Creatine deficiency syndrome /
GAMT gene /
Intellectual disability /
Epilepsy /
Gene mutation /
Child
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参考文献
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基金
中国抗癫痫协会“新锐酮学”研究项目基金(CX-A-2021-17)。