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.We developed a liquid chromatography tandem mass spectrometry (LC–MS/MS) based screen for Snyder–Robinson syndrome.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.We developed an effective LC–MS/MS diagnostic test for Snyder–Robinson syndrome.