Systematic assessment of urinary hydroxy-oxo-glutarate for diagnosis and follow-up of primary hyperoxaluria type III

Background There are currently three distinct autosomal recessive inherited types of primary hyperoxaluria (PH: PHI, PHII, and PHIII), all characterized by the endogenous overproduction of oxalate. The PH type is difficult to differentiate by clinical features alone. In addition to universal general characteristics to all hyperoxaluria subtypes, specific urinary metabolites can be detected: glycolate in PHI, L-glyceric acid in PHII, and hydroxy-oxo-glutarate (HOG) in PHIII. PHIII is considered to be the most benign form and is characterized by severe recurrent urolithiasis in early life, followed by clinical remission in many, but not all patients. We examined urinary HOG (U-HOG) excretion as a diagnostic marker and its correlation to progression of the clinical course of PHIII. Methods U-HOG was analyzed by combined ion chromatography/ mass spectrometry (IC/MS) in urine samples from 30 PHIII and 68 PHI/II patients and 79 non-PH hyperoxaluria patients. Results Mean U-HOG excretion was significantly higher in patients with PHIII than in those with PHI/II and in non-PH patients(51.6 vs. 6.61 vs. 8.36 mu mol/1.73 m(2)/24 h, respectively; p< 0.01). Conclusions Significantly elevated UHOG excretion was exclusively seen in PHIII patients and showed a 100 % consensus with the results of hydroxy-oxo-glutarate aldolaseHOGA1) mutational analysis in newly diagnosed patients. However, U-HOG excretion did not correlate with clinical course on follow-up and could not be used to discriminate between active stone formers and patients with a clinically uneventful follow-up.