New approaches towards laboratory diagnosis of isolated sulphite oxidase deficiency.

BACKGROUND Molybdenum cofactor deficiency (resulting in combined deficiencies of the enzymes sulphite oxidase, xanthine dehydrogenase and aldehyde dehydrogenase) and isolated sulphite oxidase deficiency are inherited metabolic diseases which follow an autosomal recessive trait of inheritance. Detection of these diseases in selective screening for inborn errors of metabolism is not easy because relevant metabolites are either not routinely determined or are unstable. METHODS We have searched for additional markers for these diseases and studied plasma total homocysteine (determined by enzyme immunoassay) and S-sulphonation of transthyretin (assessed by electrospray ionization mass spectrometry). RESULTS AND CONCLUSION We found total homocysteine concentrations below the limit of quantification (<1 micromol/L) in all samples of patients with sulphite oxidase deficiency studied in this regard and that the proportion of S-sulphonated transthyretin is clearly increased in such samples. Our observations suggest additional tools for selective screening and diagnostic work-up of patients suspected of having sulphite oxidase deficiency.