Heussinger Nicole, Saake Marc, Mennecke Angelika, Dörr Helmuth-Günther, Trollmann Regina
Department of Pediatrics, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
Department of Radiology, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
Pediatr Neurol. 2017 Feb;67:45-52. doi: 10.1016/j.pediatrneurol.2016.10.007. Epub 2016 Oct 17.
The X-linked creatine transporter deficiency (CRTD) caused by an SLC6A8 mutation represents the second most common cause of X-linked intellectual disability. The clinical phenotype ranges from mild to severe intellectual disability, epilepsy, short stature, poor language skills, and autism spectrum disorders. The objective of this study was to investigate phenotypic variability in the context of genotype, cerebral creatine concentration, and volumetric analysis in a family with CRTD.
The clinical phenotype and manifestations of epilepsy were assessed in a Caucasian family with CRTD. DNA sequencing and creatine metabolism analysis confirmed the diagnosis. Cerebral magnetic resonance imaging (cMRI) with voxel-based morphometry and magnetic resonance spectroscopy was performed in all family members.
An SLC6A8 missense mutation (c.1169C>T; p.Pro390Leu, exon 8) was detected in four of five individuals. Both male siblings were hemizygous, the mother and the affected sister heterozygous for the mutation. Structural cMRI was normal, whereas voxel-based morphometry analysis showed reduced white matter volume below the first percentile of the reference population of 290 subjects in the more severely affected boy compared with family members and controls. Normalized creatine concentration differed significantly between the individuals (P < 0.005).
There is a broad phenotypic variability in CRTD even in family members with the same mutation. Differences in mental development could be related to atrophy of the subcortical white matter.
由SLC6A8突变引起的X连锁肌酸转运体缺乏症（CRTD）是X连锁智力障碍的第二大常见病因。临床表型范围从轻度到重度智力障碍、癫痫、身材矮小、语言能力差和自闭症谱系障碍。本研究的目的是在一个患有CRTD的家系中，研究基因型、脑肌酸浓度和体积分析背景下的表型变异性。
对一个患有CRTD的白种人家系的临床表型和癫痫表现进行评估。DNA测序和肌酸代谢分析确诊了该病。对所有家庭成员进行了基于体素形态学和磁共振波谱的脑磁共振成像（cMRI）检查。
在五名个体中的四名中检测到SLC6A8错义突变（c.1169C>T；p.Pro390Leu，第8外显子）。两名男性同胞为半合子，母亲和患病姐妹为该突变的杂合子。结构性cMRI正常，而基于体素形态学分析显示，与家庭成员和对照组相比，病情较重的男孩的白质体积低于290名受试者参考人群的第一个百分位数。个体间的标准化肌酸浓度差异显著（P < 0.005）。
即使在具有相同突变的家庭成员中，CRTD也存在广泛的表型变异性。智力发育的差异可能与皮质下白质萎缩有关。
