Comprehensive screening of urine samples for inborn errors of metabolism by electrospray tandem mass spectrometry.
BACKGROUND
Detection of abnormal metabolites in urine is important for the diagnosis of many inborn errors of metabolism (IEM). Rapid, comprehensive screening methods are needed.


METHODS
We used electrospray ionization tandem mass spectrometry in positive- and negative-ion modes to detect selected metabolites in urine. For positive-ion analysis, samples were dried and butylated, whereas for negative-ion analysis, samples were merely diluted with the mobile phase. Analysis was by direct injection with multiple reaction monitoring for 32 metabolites in positive mode (amino acids and acylcarnitines) and 30 metabolites in negative mode (organic acids). Run time was 2.1 min in each mode.


RESULTS
Interbatch CVs ranged from 4.8% to 32%, enabling quantification of many metabolites. The procedure was applied to controls (278 and 120 in positive- and negative-ion mode, respectively) and 108 IEM individuals representing 37 different IEM. In 105 IEM individuals, representing 36 different IEM, concentrations of one or more diagnostic metabolites were above the 99th percentiles of the control values.


CONCLUSIONS
The procedure is faster and less labor-intensive than conventional methods of testing for IEM by amino and organic acid profiling and has similar diagnostic sensitivity. The ability to include a greater range of metabolites offers the potential of a more comprehensive screening procedure.
Pitt
James J
JJ
Genetic Health Services Victoria, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville 3052, Australia. jpitt@cryptic.rch.unimelb.edu.au
Eggington
Mary
M
Kahler
Stephen G
SG
D000596:Amino Acids / Q000652:urine*; D002264:Carboxylic Acids / Q000652:urine*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000652:urine*; D006801:Humans; D008403:Mass Screening; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000652:urine*; D021241:Spectrometry, Mass, Electrospray Ionization
D000596:Amino Acids; D002264:Carboxylic Acids; C116917:acylcarnitine; D002331:Carnitine