Creatine transporter defect diagnosed by proton NMR spectroscopy in males with intellectual disability.
Creatine transporter defect diagnosed by proton NMR spectroscopy in males with intellectual disability.
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DOI：
10.1002/ajmg.a.34208
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发表时间：
2011-10
影响因子：
2
通讯作者：
Renieri, Alessandra
中科院分区：
文献类型：
--
作者：
Mencarelli, Maria Antonietta;Tassini, Maria;Pollazzon, Marzia;Vivi, Antonio;Calderisi, Marco;Falco, Michele;Fichera, Marco;Monti, Lucia;Buoni, Sabrina;Mari, Francesca;Engelke, Udo;Wevers, Ron A.;Hayek, Joussef;Renieri, Alessandra
X连锁SLC 6A 8基因突变引起的肌酸缺乏综合征可导致非特异性智力残疾。诊断不能建立在临床上的理由，往往是基于评估脑肌酸水平的磁共振波谱（MRS）。考虑到MRS的高成本和镇静的必要性，该技术不能用作第一级筛选测试。同样，基因测试分析是耗时的，并且不容易被所有实验室获得。在这篇文章中，通过核磁共振（NMR）进行的尿液分析（肌酐/肌酐（Cr/Crn）比值）作为一级筛选试验的可行性进行了探讨。在进行系统的病例选择之前，显示了进一步分子分析的初步研究。测量了患有ID但无临床可识别综合征的男性患者（n = 1，347）的NMR尿液光谱。根据Cr/Crn比值异常，选择3例具有最高值的患者进行分子分析。两名患者的第二次尿检结果为阳性，诊断通过脑肌酸水平降低和SLC 6A 8基因分析得到进一步证实。在其中一个中发现了一个新生突变。另一名患者从母亲那里继承了一种新的突变，她也有轻度的ID。第三名患者的重复尿检呈阴性，因此大脑中的肌酸水平和SLC 6A 8基因分析都得到了正常的结果。我们的结论是，Cr/Crn比测定男性患者的NMR代表了一个快速和有用的第一级筛选测试分子分析之前。© 2011 Wiley-Liss公司。
Creatine deficiency syndrome due to mutations in X-linked SLC6A8 gene results in nonspecific intellectual disability (ID). Diagnosis cannot be established on clinical grounds and is often based on the assessment of brain creatine levels by magnetic resonance spectroscopy (MRS). Considering high costs of MRS and necessity of sedation, this technique cannot be used as a first level-screening test. Likewise, gene test analysis is time consuming and not easily accessible to all laboratories. In this article feasibility of urine analysis (creatine/creatinine (Cr/Crn) ratio) performed by nuclear magnetic resonance (NMR) as a first level-screening test is explored. Before running a systematic selection of cases a preliminary study for further molecular analysis is shown. NMR urine spectra (n = 1,347) of male patients with an ID without a clinically recognizable syndrome were measured. On the basis of abnormal Cr/Crn ratio, three patients with the highest values were selected for molecular analysis. A confirmatory second urine test was positive in two patients and diagnosis was further confirmed by a decreased brain creatine level and by SLC6A8 gene analysis. A de novo mutation was identified in one. Another patient inherited a novel mutation from the mother who also has a mild ID. A repeat urine test was negative in the third patient and accordingly creatine level in the brain and SLC6A8 gene analysis both gave a normal result. We conclude that Cr/Crn ratio measured by NMR for male patients represents a rapid and useful first level screening test preceding molecular analysis. © 2011 Wiley-Liss, Inc.
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影响因子：
9.8
作者：
Salomons, GS;van Dooren, SJM;Jakobs, C
通讯作者：
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作者：
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