A family with creatine deficiency syndrome due to SLC6A8 gene novel mutation / 中华实用儿科临床杂志

ABSTRACT

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.