Spurious Elevation of Multiple Urine Amino Acids by Ion-Exchange Chromatography in Patients with Prolidase Deficiency

  • Carlos R. FerreiraEmail author
  • Kristina Cusmano-Ozog
Case Report
Part of the JIMD Reports book series (JIMD, volume 31)


The enzyme prolidase cleaves dipeptides where the C-terminal amino acid corresponds to proline or hydroxyproline. As a consequence, a deficiency of this enzyme leads to accumulation of these dipeptides, which correspondingly are found to be elevated in urine. In fact, the absence of dipeptiduria is sufficient to rule out a diagnosis of prolidase deficiency. However, given the fact that these dipeptides elute at the same position as more common amino acids, the analyzer’s software will instead call an elevation of these corresponding amino acids. Thus, an elevation of glycylproline, aspartylproline, glutamylproline, threonylproline and serylproline, valylproline, leucylproline, isoleucylproline, alanylproline, phenylalanylproline, and lysylproline will instead be interpreted as an elevation of leucine, citrulline, methionine, isoleucine, beta-aminoisobutyric acid, gamma-aminobutyric acid, ethanolamine, tyrosine, histidine, and anserine/carnosine, respectively. This particular profile of elevated amino acids, however, can easily be overlooked. We hope that the recognition of this characteristic pattern of falsely elevated urinary amino acids will aid in the recognition of prolidase deficiency.


Intellectual Disability Multiple Amino Acid Urine Amino Acid Tall Peak Canonical Splice Site 
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Supplementary material

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.National Human Genome Research Institute, National Institutes of HealthBethesdaUSA
  2. 2.Children’s National Health SystemWashington, DCUSA

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