Creatine transporter defect diagnosed by proton NMR spectroscopy in males with intellectual disability.
Bottom Line: 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 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.
Affiliation: Medical Genetics, Department of Biotechnology, University of Siena, Italy.Show MeSH
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Mentions: As no age- and sex-related reference values are available for the Cr/Crn ratio in urine we derived reference intervals (p5, 50, and 95) from our total patient group. The data did not show a Gaussian distribution and this was also not the case after logarithmic transformation. To obtain the reference intervals shown in Table I a bootstrap resampling procedure was used for data of which the distribution is not known. The dataset was split in age group classes (0–5, 6–10, 11–15, 16–20, and >20 years) (Fig. 1). Within each class we performed bootstrap resampling (n = 1,000). Bootstrap statistical techniques are computer intensive methods falling in the resampling techniques used as an alternative based parametric statistic (p < 0,05). Adèr et al.  recommended the use of bootstrapping procedures when the theoretical distribution of a statistic is complicated or unknown. As the bootstrapping procedure is distribution-independent, it provides an indirect method to assess the properties of the distribution underlying the sample and the parameters of interest. There was an obvious age and sex relation of the data. Subsequently the three male patients with the highest Cr/Crn ratio were selected. The ratio was consistently abnormal in two patients but two repeat samples in patient three showed normal results (Fig. 2; Table I).
Affiliation: Medical Genetics, Department of Biotechnology, University of Siena, Italy.