Primary Hyperoxaluria

GC-MS assay may offer more precise screening for pediatric primary hyperoxaluria

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The development of a highly sensitive gas chromatography-mass spectrometry (GC-MS) assay for measuring plasma oxalate levels holds promise for screening and monitoring primary hyperoxaluria, particularly in pediatric patients, according to a study.

The assay demonstrated impressive precision and sensitivity, establishing cut-off values for distinguishing primary from non-primary hyperoxaluria in pediatric populations. The study also highlighted the importance of interpreting oxalate concentrations in a clinical context, given potential sources of interference.

The methodology behind this assay involves the extraction, derivatization, and subsequent analysis of plasma oxalate. Researchers honed in on specific ions for precise quantification, using m/z 261.10 for oxalate and m/z 263.15 for the internal standard, 13C2-oxalate.

Method validation was rigorous, encompassing essential parameters like linear range, limit of blank, limit of detection, lower limit of quantification, precision, recovery, carryover, interference, and dilution effect. The results were highly promising, with a detection limit of 0.78 μmol/L and a linear range extending up to 80.0 μmol/L.

The assay demonstrated excellent precision, with between-day variations of 5.7% at 41.3 μmol/L and 13.1% at 1.6 μmol/L. Carryover was minimal, at less than 0.2%, while the recovery rate fell within the range of 90% to 110%. The study also identified potential sources of interference, notably intralipids and bilirubin, which caused false elevations of oxalate concentrations.

A pivotal outcome of the study was the establishment of cut-off values for distinguishing primary from non-primary hyperoxaluria in pediatric patients. A threshold of 13.9 μmol/L exhibited 63% specificity and 77% sensitivity, while a cut-off of 4.15 μmol/L demonstrated 100% specificity but lower sensitivity at 20%.

Furthermore, the assay necessitated a minimum sample volume of 250 μL, offering practicality in clinical settings. It’s worth noting that detected oxalate concentrations could be influenced by various factors, including instrument conditioning, sample preparation procedures, medications, and underlying clinical conditions.

Yazdanpanah M, Cameron J, Chappel C, Yuan L. Primary Hyperoxaluria Screening and Monitoring: Quantitative Measurement of Plasma Oxalate by Gas Chromatography-Mass Spectrometry With High Sensitivity. Ann Lab Med. 2023;doi: 10.3343/alm.2023.0178. Epub ahead of print. PMID: 37904578.