How to Cite this Article: Mencarelli MA, Tassini M, Pollazzon M, Vivi A, Calderisi M, Falco M, Fichera M, Monti L, Buoni S, Mari F, Engelke U, Wevers RA, Hayek J, Renieri A. 2011. Creatine transporter defect diagnosed by proton NMR spectroscopy in males with intellectual disability. Am J Med Genet Part A 155:2446–2452.
Article first published online: 9 SEP 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 10, pages 2446–2452, October 2011
How to Cite
Mencarelli, M. A., Tassini, M., Pollazzon, M., Vivi, A., Calderisi, M., Falco, M., Fichera, M., Monti, L., Buoni, S., Mari, F., Engelke, U., Wevers, R. A., Hayek, J. and Renieri, A. (2011), Creatine transporter defect diagnosed by proton NMR spectroscopy in males with intellectual disability. Am. J. Med. Genet., 155: 2446–2452. doi: 10.1002/ajmg.a.34208
Maria Antonietta Mencarelli and Maria Tassini contributed equally to this work.
- Issue published online: 20 SEP 2011
- Article first published online: 9 SEP 2011
- Manuscript Accepted: 23 JUN 2011
- Manuscript Received: 7 JAN 2011
- Re-use of this article is permitted in accordance with the Terms and Conditions set out at [http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms]
- Telethon. Grant Numbers: GTB07001, GP06170
- creatine deficiency syndrome;
- magnetic resonance spectroscopy;
- NMR urine
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.