Extraction of glyceric and glycolic acids from urine with tetrahydrofuran: utility in detection of primary hyperoxaluria

Abstract

Primary hyperoxaluria (PH) is an autosomal recessive metabolic abnormality characterized by excessive oxalate excretion leading to nephrocalcinosis and progressive renal dysfunction. Type I primary hyperoxaluria (PH I) results from a deficiency of alanine:glyoxylate aminotransferase, whereas type II disease has been traced to a deficiency of d-glycerate dehydrogenase. The two syndromes are often distinguished on the basis of organic acids that are coexcreted with oxalate: glycolate and l-glycerate in type I and type II disease, respectively. Routine organic acid analysis with diethyl ether extraction followed by gas chromatographic analysis failed to detect normal and increased concentrations of these diagnostic metabolites. Subsequent extraction of urine with tetrahydrofuran (THF), however, extracted 75% of added glycerate, 42% of added glycolate, and 75% of added ethylphosphonic acid (internal calibrator). THF extraction was analytically sensitive enough to allow determination of normal excretion of glycolate (14–72 μg/mg creatinine) and glycerate (0–5 years, 12–177 μg/mg creatinine and >5 years, 19–115 μg/mg creatinine). Four of five patients with PH I and both patients with type II disease were correctly identified. Thus, THF extraction is a convenient adjunct to routine organic acid analysis and facilitates the detection of PH.

Simultaneous analysis of urinary metabolites for preliminary identification of primary hyperoxaluria

“…In addition, there has been a recent report of elevated urine glycolate as the result of GO deficiency, although this disorder appears to be an incidental finding without a clinical phenotype. 30 The range of glycolate:creatinine ratios in the control group in this dataset was similar to previously reported ranges by a variety of methods: 20-107 mol/mmol by GCMS, 12 13-80 and 13-90 mol/mmol by ion-chromatography, 29,31 22-125 mol/mmol by chromotropic acid 32 but was somewhat higher than the levels reported using GO (4-41 mol/mmol). 33 This suggests that the positive bias we found with respect to the GO method may be attributed to under-recovery of glycolate by GO.…”

Rapid liquid chromatography tandem mass-spectrometry screening method for urinary metabolites of primary hyperoxaluria

“…The glycolate:creatinine ratios in PH1 patients and controls produced by our method were similar to those previously reported. [10][11][12] Glycolate was not a completely sensitive nor specific marker for PH1 since not all PH1 patients had elevated levels -a finding that has been previously documented. 7 This situation possibly reflects inter-individual variation of enzymes including glycolate oxidase, LDH and GR involved in endogenous glycolate and glyoxylate metabolism as well as a dietary contribution.…”

Quantification of glycolic acid in cosmetic products using reversed phase high performance liquid chromatography

“…Methods for glycolic acid quantification in serum have been reported, because glycolic acid is a metabolite of ethylene glycol [25–27], dichloroacetic acid [28], dichloroethane [29], and glycolate‐based polymers used for drug delivery [30, 31]. Glycolic acid is a useful indicator of hyperoxaluria [32, 33]. The detection of glycolic acid in body fluids has also been achieved using enzymatic conversion to glyoxylate and detection following phenylhydrazine derivatization [34].…”