RESUMO
Molybdenum cofactor and isolated sulphite oxidase deficiencies are two related rare autosomal recessive diseases characterized by severe neurological abnormalities, dislocated lens and mental retardation. Determination of three biochemical markers S-sulphocysteine (SSC), xanthine (XAN) and hypoxanthine (HXAN) in urine is essential for a definitive diagnosis and identification of the exact defect. We developed a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of SSC, XAN and HXAN in urine. The analysis was carried out in the negative-ion selected-reaction monitoring mode. The turnaround time for the assay was 7 min. Linear calibration curves for the three biomarkers were obtained in the range of 12-480 micromol/L. The intra- and inter-day assay variations were <2.5%. Mean recoveries of SSC, XAN and HXAN added to urine at two significantly different concentrations were in the range 94.3-107.3%. At a normal SSC urine excretion value of 3.2 micromol/mmol creatinine, the signal-to-noise ratio was 337:1. This stable isotope dilution LC-MS/MS method is specific, rapid and simple, and provides definitive diagnosis for molybdenum cofactor and isolated sulphite oxidase deficiencies in very small volumes of urine. We have identified seven new cases of isolated sulphite oxidase deficiency from four Saudi families and one Sudanese family.