High-throughput urine screening for Smith-Lemli-Opitz syndrome and cerebrotendinous xanthomatosis using negative electrospray tandem mass spectrometry

Abstract

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) and cerebrotendinous xanthomatosis (CTX) are disorders affecting cholesterol metabolism. Currently, diagnosis relies on clinical recognition and specific and complex biochemical testing. METHODS: A rapid, high-throughput urine test, suitable for mass screening for these two disorders, was developed using flow injection negative electrospray tandem mass spectrometry with multiple reaction monitoring. Cholestane-pentol glucuronide, a known marker for CTX, was measured and a steroid sulfate with a proposed keto-pregnadien-diol structure was identified and measured for SLOS. Measurement of the two markers was readily incorporated into an existing tan..