Thurm Audrey, Himelstein Daniel, DʼSouza Precilla, Rennert Owen, Jiang Susanqi, Olatunji Damilola, Longo Nicola, Pasquali Marzia, Swedo Susan, Salomons Gajja S, Carrillo Nuria
*Pediatrics and Developmental Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD; †Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; ‡Therapeutics for Rare and Neglected Diseases, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD; §Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT; ‖Associated Regional and University Pathologists (ARUP) Laboratories, Salt Lake City, UT; ¶Department of Pathology, University of Utah, Salt Lake City, UT; **Department of Clinical Chemistry, Metabolic Unit, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
J Dev Behav Pediatr. 2016 May;37(4):322-6. doi: 10.1097/DBP.0000000000000299.
Creatine transporter deficiency (CTD) is an X-linked, neurometabolic disorder associated with intellectual disability that is characterized by brain creatine (Cr) deficiency and caused by mutations in SLC6A8, the Cr transporter 1 protein gene. CTD is identified by elevated urine creatine/creatinine (Cr/Crn) ratio or reduced Cr peak on brain magnetic resonance spectroscopy; the diagnosis is confirmed by decreased Cr uptake in cultured fibroblasts, and/or identification of a mutation in the SLC6A8 gene. Prevalence studies suggest this disorder may be underdiagnosed. We sought to identify cases from a well-characterized cohort of children diagnosed with neurodevelopmental disorders.
Urine screening for CTD was performed on a cohort of 46 males with autism spectrum disorder (ASD) and 9 males with a history of non-ASD developmental delay (DD) classified with intellectual disability.
We identified 1 patient with CTD in the cohort based on abnormal urine Cr/Crn, and confirmed the diagnosis by the identification of a novel frameshift mutation in the SLC6A8 gene. This patient presented without ASD but with intellectual disability, and was characterized by a nonspecific phenotype of early language delay and DD that persisted into moderate-to-severe intellectual disability, consistent with previous descriptions of CTD.
Identification of patients with CTD is possible by measuring urine Cr and Crn levels and the current case adds to the growing literature of neurocognitive deficits associated with the disorder that affect cognition, language and behavior in childhood.
肌酸转运体缺乏症（CTD）是一种X连锁的神经代谢障碍疾病，与智力残疾相关，其特征为脑内肌酸（Cr）缺乏，由肌酸转运体1蛋白基因SLC6A8的突变引起。CTD通过尿肌酸/肌酐（Cr/Crn）比值升高或脑磁共振波谱中Cr峰降低来识别；通过培养的成纤维细胞中Cr摄取减少和/或SLC6A8基因中突变的鉴定来确诊。患病率研究表明这种疾病可能未得到充分诊断。我们试图从一组特征明确的被诊断为神经发育障碍的儿童中识别病例。
对一组46名患有自闭症谱系障碍（ASD）的男性和9名有非ASD发育迟缓（DD）病史且伴有智力残疾的男性进行了CTD的尿液筛查。
我们根据异常的尿Cr/Crn在该队列中识别出1例CTD患者，并通过鉴定SLC6A8基因中的一个新的移码突变确诊。该患者没有ASD表现，但有智力残疾，其特征为早期语言发育迟缓及DD的非特异性表型，持续发展为中度至重度智力残疾，与先前对CTD的描述一致。
通过测量尿Cr和Crn水平可以识别CTD患者，当前病例增加了与该疾病相关的影响儿童认知、语言和行为的神经认知缺陷的文献报道。
