大脑肌酸缺乏综合征1例报告并文献复习

Cerebral creatine deficiency syndromes： a case report and literature review

目的探讨大脑肌酸缺乏综合征（CCDS）的诊断及治疗要点，提高对CCDS的认识。方法报道1例CCDS患者的临床资料，并结合相关文献进行回顾性分析。结果本例患者为青年男性，临床表现为智力障碍、语言发育迟缓、癫痫发作、性格孤僻等。头颅MRI提示右侧大脑半球发育小，左侧大脑半球脑回、脑白质发育异常，胼胝体发育异常。脑电图提示双侧额、中央、颞导联可见棘波、多棘波、多棘慢波暴发与4～5Hz慢波交替出现。基因检测提示患者携带GAMT基因C．242C〉T（P．A81V）杂合错义突变。诊断为CCDS。经补充肌酸、抗癫痫、营养神经等治疗后，未有癫痫发作，但是记忆力、计算力、理解力等高级皮质功能改善不明显。结论患者表现为生长发育迟缓、智力缺陷和严重的言语障碍等症状时，要考虑到CCDS可能。对此类患者应及早行AGAT、GAMT和SLC6A8基因检测，以明确诊断、及早干预。

Objective To discuss the diagnosis and treatment key points of cerebral creatine deficiency syndromes （CCDS） to improve the understanding of the disease. Methods A retrospective study was performed to analyze the clinical data from one patient with CCDS, in accordance with relevant literature. Results This patient was a young men who presented intellectual disabilities, language development delay, seizures and autism spectrum disorders. Brain MRI re- vealed brain atrophy in the right hemisphere and abnormal development in the gyms and white matter in the left hemi- sphere and the corpus callosum. Electroencephalography （EEG） showed alternating bursts of spike waves, multiple spike waves and multiple spike slow waves and 4 - 5 Hz slow waves in the bilateral frontal, central and temporal cortex. Ac- cording to genetic testing, he carried GAMT gene with a heterozygous missense mutation of c. 242C 〉 T （p. A81V）. The patient was diagnosed with cerebral creatine deficiency syndromes. After treated with oral creatine, antiepileptic drugs and neurotrophic medicines, his seizure disorder was controlled, but no obvious improvements were observed in higher cortical function, such as memory, calculation skills and understanding. Conclusions It is necessary to consider CCDS when patients show developmental delay, intellectual deficiency and severe dysphonia. It is necessary for these patients to undergo early genetic measurement of AGAT, GAMT and SLC6A8 for clear diagnosis and early interference.