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

Clin Chim Acta. 2011 Mar 18;412(7-8):655-60. doi: 10.1016/j.cca.2010.12.037. Epub 2011 Jan 8.

Abstract

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.

Publication types

  • Validation Study

MeSH terms

  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid / methods*
  • Humans
  • Spermine Synthase / genetics*
  • Tandem Mass Spectrometry / methods*
  • X-Linked Intellectual Disability / diagnosis*

Substances

  • Spermine Synthase

Supplementary concepts

  • Snyder Robinson syndrome