title: High-throughput tandem mass spectrometry multiplex analysis for newborn urinary screening of creatine synthesis and transport disorders, Triple H syndrome and OTC deficiency.
abstract: BACKGROUND
  Creatine synthesis and transport disorders, Triple H syndrome and ornithine transcarbamylase deficiency are treatable inborn errors of metabolism. Early screening of patients was found to be beneficial. Mass spectrometry analysis of specific urinary biomarkers might lead to early detection and treatment in the neonatal period. We developed a high-throughput mass spectrometry methodology applicable to newborn screening using dried urine on filter paper for these aforementioned diseases.
  
  
  METHODS
  A high-throughput methodology was devised for the simultaneous analysis of creatine, guanidineacetic acid, orotic acid, uracil, creatinine and respective internal standards, using both positive and negative electrospray ionization modes, depending on the compound.
  
  
  RESULTS
  The precision and accuracy varied by <15%. Stability during storage at different temperatures was confirmed for three weeks. The limits of detection and quantification for each biomarker varied from 0.3 to 6.3 μmol/l and from 1.0 to 20.9 μmol/l, respectively. Analyses of urine specimens from affected patients revealed abnormal results. Targeted biomarkers in urine were detected in the first weeks of life.
  
  
  CONCLUSIONS
  This rapid, simple and robust liquid chromatography/tandem mass spectrometry methodology is an efficient tool applicable to urine screening for inherited disorders by biochemical laboratories.
authors.affiliation: Service of Genetics, Dept. of Pediatrics, Faculty of Medicine and Health Sciences, 3001, 12th Avenue North, Université de Sherbrooke, Sherbrooke J1H 5N4, QC Canada. Electronic address: christiane.auray-blais@usherbrooke.ca.
authors.forename: Christiane
authors.initials: C
authors.lastname: Auray-Blais
authors.affiliation: Service of Genetics, Dept. of Pediatrics, Faculty of Medicine and Health Sciences, 3001, 12th Avenue North, Université de Sherbrooke, Sherbrooke J1H 5N4, QC Canada.
authors.forename: Bruno
authors.initials: B
authors.lastname: Maranda
authors.affiliation: Service of Genetics, Dept. of Pediatrics, Faculty of Medicine and Health Sciences, 3001, 12th Avenue North, Université de Sherbrooke, Sherbrooke J1H 5N4, QC Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Lavoie
mesh_terms: D015415:Biomarkers / Q000652:urine; D003401:Creatine / Q000652:urine; D003404:Creatinine / Q000652:urine; D005374:Filtration; D005998:Glycine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D022124:Hyperammonemia / Q000175:diagnosis* / Q000652:urine*; D007231:Infant, Newborn; D009952:Ornithine / Q000172:deficiency* / Q000652:urine; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000175:diagnosis* / Q000652:urine*; D009963:Orotic Acid / Q000652:urine; D010209:Paper; D012016:Reference Values; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards; D014498:Uracil / Q000652:urine; D056806:Urea Cycle Disorders, Inborn / Q000175:diagnosis* / Q000652:urine*; D016482:Urinalysis / Q000379:methods* / Q000592:standards
chemical_list: D015415:Biomarkers; D014498:Uracil; D009963:Orotic Acid; D003404:Creatinine; D009952:Ornithine; C004946:glycocyamine; D003401:Creatine; D005998:Glycine
keywords: Creatine synthesis and transport disorders; Mass spectrometry; Newborn screening; OTC deficiency; Triple H syndrome; Urine dried on filter paper