SLC6A8基因新发突变致肌酸缺乏综合征一家系

A family with creatine deficiency syndrome due to SLC6A8 gene novel mutation

对2018年9月新乡医学院第一附属医院儿科确诊的 SLC6A8基因突变致肌酸缺乏综合征(CDS)一家系的临床特征、遗传学和生化特点进行分析。患儿,男,初诊时13岁,因"间断呕吐1年"就诊,对症支持治疗后好转,间隔7个月,再次发病住院确诊。自幼进食少,便秘。12岁始出现呕吐伴严重便秘,间断发作。患儿1岁6个月会走。2岁会叫爸妈,检查时只会说简单句子。很少与父母交流。其兄有严重智力障碍和癫痫。其母存在认知功能障碍,有反复死产和流产史。初诊患儿查体:体质量22 kg(< P3),身高131 cm(< P3),头围52 cm,重度智力障碍,表情呆滞,交流困难,宽前额,骨骼肌萎缩,弓形足。头颅磁共振成像示患儿双侧侧脑室轻度对称性扩大。脑磁共振波谱检查示患儿双侧海马未见异常。智力障碍相关基因测序发现,患儿 SLC6A8基因c.626(exon3)-c.627(exon3)delCT半合子突变,其母及兄均携带该变异基因,其父及外祖母均无该基因突变。患儿尿肌酸/肌酐比值增高,胍基乙酸正常,进一步证实 SLC6A8基因新发位点移码突变致CDS。临床上遇到不明原因智力障碍男童,反复出现胃肠道症状,尤其是婴儿期出现喂养困难及生长发育迟缓时,行尿胍基乙酸和肌酸/肌酐比值测定筛查及基因检测可早期诊断CDS。

To analyze the clinical,molecular genetic and biochemical characteristics of a family diagnosed with creatine deficiency syndrome(CDS)due to SLC6A8 gene mutation diagnosed in Department of Pediatrics,the First Affiliated Hospital of Xinxiang Medical University in September 2018.The boy was referred at the age of 13 for intermittent vomiting and symptoms were relieved after symptomatic treatment,7 months later,the patient was diagnosed again.He ate less and constipated as an infant,and had intermittent vomiting and severe constipation from 12 years old.He could walk at the age of 1 year and 6 months,could speak his first word at 2 years old,and only spoke simple sentences at the diagnosis.He rarely communicated with his parents.His brother has severe intellectual deficiency and seizures.His mother has cognitive impairment and had repeated stillbirths and miscarriages.When visiting the doctor,his weight was 22 kg(<P3),height was 131 cm(<P3),and head circumference was 52 cm.Besides,he had severe mental retardation and sluggish expression,poor communication,broad forehead,musculoskeletal atrophy and arched foots.His brain magnetic resonance imaging showed mild enlargement of the lateral ventricles.Magnetic resonance spectroscopy showed normal signals in the bilateral hippocampuses.The boy′s exon sequencing related to intellectual deficiency revealed the hemizygous mutation of SLC6A8 gene c.626(exon3)-c.627(exon3)delCT.His mother and brother were carriers of the variant gene,but his father and grandmother had no such mutation.The urinary creatine to creatinine ratio was elevated but guanidinoacetate was normal,it was further confirmed that CDS can be caused by the novel mutation c.626(exon3)-c.627(exon3)delCT in SLC6A8.In clinical practice,boy with mental retardation of unknown origin and often have gastrointestinal symptoms,especially when feeding difficulties and growth retardation occur in infancy,the early diagnosis of CDS can be achieved by examination of urinary creatine to creatinine ratio and gene detection.