Open Access

BACKGROUND Clinical presentation and disease severity in disorders of purine and pyrimidine metabolism vary considerably. We present a method that allows comprehensive, sensitive, and specific diagnosis of the entire spectrum of abnormalities in purine and pyrimidine metabolism in 1 analytical run. METHODS We used reversed-phase HPLC electrospray ionization tandem mass spectrometry to investigate 24 metabolites of purine and pyrimidine metabolism in urine samples from healthy persons and from patients with confirmed diagnoses of inherited metabolic disorders. Urine samples were filtered and diluted to a creatinine concentration of 0.5 mmol/L. Stable-isotope-labeled internal standards were used for quantification. The metabolites were analyzed by multiple-reaction monitoring in positive and negative ionization modes. RESULTS Total time of analysis was 20 min. Recovery (n = 8) of a compound after addition of a known concentration was 85%-133%. The mean intraday variation (n = 10) was 12%. The interday variation (n = 7) was < or =17%. Age-related reference intervals were established for each compound. Analysis of patient urine samples revealed major differences in tandem mass spectrometry profiles compared with those of control samples. Twelve deficiencies were reliably detected: hypoxanthine guanine phosphoribosyl transferase, xanthine dehydrogenase, purine nucleoside phosphorylase, adenylosuccinate lyase, uridine monophosphate synthase, adenosine deaminase, adenine phosphoribosyl transferase, molybdenum cofactor, thymidine phosphorylase, dihydropyrimidine dehydrogenase, dihydropyrimidinase, and beta-ureidopropionase. CONCLUSION This method enables reliable detection of 13 defects in purine and pyrimidine metabolism in a single analytical run.

Grailog embodies a systematics to visualize knowledge sources by graphical elements. Its main benefit is that the resulting visual presentations are easier to read for humans than the original symbolic source code. In this paper we introduce a methodology to handle the mapping from Datalog RuleML, serialized in XML, to an SVG representation of Grailog, also serialized in XML, via eXtensible Stylesheet Language Transformations (XSLT) 2.0/XML; the SVG is then rendered visually by modern Web browsers. This initial mapping is realized to target Grailog's "fully node copied" normal form. Elements can thus be translated one at a time, separating the fundamental Datalog-to-SVG translation concern from the concern of merging node copies for optimal (hyper)graph layout and avoiding its high computational complexity in this online tool. The resulting open source Grailog Knowledge-Source Visualizer (Grailog KS Viz) supports Datalog RuleML with positional relations of arity n>1. The on-the-fly transformation was shown to run on all recent major Web browsers and should be easy to understand, use, and extend.