Methods for the diagnosis of creatine deficiency syndromes: a comparative study

J Neurosci Methods. 2006 Sep 30;156(1-2):305-9. doi: 10.1016/j.jneumeth.2006.03.005. Epub 2006 Apr 18.

Abstract

The increasing number of patients with creatine deficiency syndromes (CDS) stresses the need to develop screening procedures for the identification these inherited disorders. Guanidinoacetate (GAA) and creatine (Cr) are reliable biochemical markers of CDS and several analytical methods to measure both metabolites have been developed. High-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) is quick and sensitive but, unlike HPLC and gas chromatography-mass spectrometry (GC/MS), it is unavailable in most laboratories. Thus, we decided to evaluate comparatively HPLC-MS/MS, GC/MS and HPLC methods, as well as to establish reference values in a healthy paediatric population. According to our results, these three methods may be suitable for analysing GAA in urine. Furthermore, Passing-Bablock plots showed good agreement among all three. However, when comparing the Cr/Crn ratio, our results revealed that while HPLC-MS/MS data were in agreement with those of GC/MS, a constant and proportional error was observed when compared with those of HPLC. Consequently, the Cr/Crn ratio obtained by the last method should be evaluated with caution. Our reference values for GAA and Cr/Crn ratio in urine negatively correlate with age. Concerning GAA and Cr measurements in plasma, it is interesting to note that in contrast to what was occurring in urine, GAA concentration increased significantly with age, while we did not find any significant difference for Cr values within the same age group.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aging / metabolism
  • Biomarkers
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid
  • Creatine / blood
  • Creatine / deficiency*
  • Creatine / urine
  • Creatinine / blood
  • Creatinine / urine
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Glycine / analogs & derivatives
  • Glycine / blood
  • Glycine / urine
  • Humans
  • Indicators and Reagents
  • Infant
  • Male
  • Mass Spectrometry
  • Purine-Pyrimidine Metabolism, Inborn Errors / blood
  • Purine-Pyrimidine Metabolism, Inborn Errors / diagnosis*
  • Purine-Pyrimidine Metabolism, Inborn Errors / urine
  • Reference Standards

Substances

  • Biomarkers
  • Indicators and Reagents
  • Creatinine
  • glycocyamine
  • Creatine
  • Glycine