Yang L, Fang F, Jin H, Wu Y
Department of Neurology, Neurological Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing100045, China.
Zhonghua Er Ke Za Zhi. 2024 Dec 2;62(12):1202-1207. doi: 10.3760/cma.j.cn112140-20240715-00485.
To analyze the clinical features of creatine transporter(CRTR) deficiency associated with SLC6A8 gene variants. The clinical data (clinical presentation, brain imaging, creatine metabolism test and gene variants) of 5 patients admitted to Beijing Children's Hospital, Capital Medical University and diagnosed with CRTR deficiency associated with SLC6A8 gene variants from January 2016 to June 2024 were retrospectively analyzed. A total of 5 patients, all male, presented with the onset of the disease at 1 year and 1 month old to 1 year and 10 months old, and diagnosis at 1 year and 3 months to 9 years old. All patients exhibited varying degrees of intellectual and physical developmental deficits, with autistic-like behaviors present in 2 patients and convulsive episodes present in 4 patients. The brain magnetic resonance imaging, of all 5 patients showed either poor or slightly delayed myelination. Additionally, the brain magnetic resonance spectroscopy (MRS) imaging of 5 patients all showed decreased creatine peaks, and 4 patients had elevated urinary creatine levels indicated by blood and (or) urine creatine metabolism tests. There were 3 patients completed blood creatinine tests, all indicating reduction. Whole-exome sequencing was conducted on all 5 patients, and 4 unreported novel variants were identified: c.371G>C, c.1017-1G>A, c.912+1G>T and c.1016+2T>A. Following treatment with creatine, arginine, and glycine supplementation, no significant advancement was observed in motor and language development. CRTR deficiency associated with SLC6A8 gene variants manifests as developmental delay with or without seizures, with atypical clinical features, the presence of decreased blood creatinine levels and elevated urinary creatine levels. Combined with brain MRS and genetic testing results, patients can be diagnosed.
分析与SLC6A8基因变异相关的肌酸转运体（CRTR）缺乏症的临床特征。回顾性分析2016年1月至2024年6月首都医科大学附属北京儿童医院收治的5例诊断为与SLC6A8基因变异相关的CRTR缺乏症患者的临床资料（临床表现、脑影像学、肌酸代谢检测及基因变异）。5例患者均为男性，发病年龄为1岁1个月至1岁10个月，确诊年龄为1岁3个月至9岁。所有患者均表现出不同程度的智力和身体发育缺陷，2例患者有类似自闭症的行为，4例患者有惊厥发作。5例患者的脑磁共振成像均显示髓鞘形成不良或略有延迟。此外，5例患者的脑磁共振波谱（MRS）成像均显示肌酸峰降低，4例患者经血液和（或）尿液肌酸代谢检测提示尿肌酸水平升高。3例患者完成血肌酐检测，均提示降低。对所有5例患者进行全外显子测序，鉴定出4个未报道的新变异：c.371G>C、c.1017-1G>A、c.912+1G>T和c.1016+2T>A。补充肌酸、精氨酸和甘氨酸治疗后，运动和语言发育未见明显进展。与SLC6A8基因变异相关的CRTR缺乏症表现为有或无癫痫发作的发育迟缓，临床特征不典型，血肌酐水平降低和尿肌酸水平升高。结合脑MRS和基因检测结果可对患者进行诊断。
