Enzymatic diagnosis of Sjögren-Larsson syndrome using electrospray ionization mass spectrometry

BackgroundSjögren-Larsson syndrome is a metabolic disorder characterized by accumulation of long-chain fatty alcohols in plasma of patients due to mutations in the ALDH3A2 gene, that codes for a microsomal fatty aldehyde dehydrogenase (FALDH). Recent studies have demonstrated that FALDH is involved in the last step of the conversion of 22-hydroxy-C22:0 into the dicarboxylic acid of C22:0 (C22:0-DCA).MethodsFALDH activity was determined by incubating fibroblast homogenates with ω-hydroxy-C22:0 in the presence of NAD+. Electrospray ionization mass spectrometry (ESI-MS) was used to quantify the amounts of C22:0-DCA produced.ResultsAll SLS patients were deficient in C22:0-DCA productions with activities ranging from 3.2–26.3% of mean control.ConclusionsThe new assay described in this paper has substantial advantages over previous assays, and allows for the easy, reliable and rapid diagnosis of SLS.