Diagnostic screening for spermine synthase deficiency by liquid chromatography tandem mass spectrometry

Background: Snyder-Robinson syndrome is an X-linked genetic disorder characterized by intellectual disability, facial asymmetry, thickened lower lip, long hands with hyper extendable fingers, slow speech, and hyposcoliosis. The disorder is caused by a mutation in the spermine synthase (SMS) gene. The SMS gene encodes an enzyme involved in polyamine metabolism. Specifically, individuals with Snyder-Robinson have lack or have diminished capability to covert spermidine to spermine. Methods: We developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) based screen for Snyder-Robinson syndrome. Results: Since individuals with Snyder-Robinson syndrome have diminished capacity to convert spermidine to spermine, we utilize this characteristic as a screening metric. Spermine to spermidine ratios were measured by LC-MS/MS in both normal controls and individuals with Snyder-Robinson syndrome. Polyamine ratios in subjects with Snyder-Robinson syndrome (n = 20) were significantly different from controls (n = 11) and carriers (n = 5), with p values of 0.0001 and 0.0075, respectively. Conclusions: We developed an effective LC-MS/MS diagnostic test for Snyder-Robinson syndrome. (C) 2011 Elsevier B.V. All rights reserved.