Neonatal urinary steroids in Smith-Lemli-Opitz syndrome associated with 7-dehydrocholesterol reductase deficiency

Cedric H L Shackleton, Esther Roitman, Richard Kelley

Research output: Contribution to journalArticle

Abstract

The biosynthetic abnormality in Smith-Lemli-Opitz syndrome (SLOS) is a deficiency of 7-dehydrocholesterol (7DHC) reductase, the enzyme responsible for catalyzing the final step in the Kandutsch-Russell pathway for cholesterol synthesis. Because the disposition of 7DHC and 8- dehydrocholesterol [8DHC; cholesta-5,8(9)-dien-3β-ol] produced in this syndrome is little understood, we have analyzed urine from three young infants by gas chromatography/mass spectrometry to characterize its steroid metabolites. All steroid metabolites of adrenal origin found in normal infant urine were also found in urine from the patients with SLOS but in reduced amount. Quantitatively, the major steroids in these SLOS patients were identified by mass spectrometry as homologs of normal neonatal steroids possessing an additional double bond. Generally, two forms of each steroid were present in a similar amount. Because of the markedly increased levels of 7DHC and 8DHC in SLOS, these almost certainly represented the 5,7 and 5,8(9) unsaturated forms of each metabolite. The most abundant steroids were tentatively identified as 3β,16α-dihydroxy-5,7-pregnadien-20-one and 3β,16α-dihydroxy-5,8(9)-pregnadien-20-one, although similar 21-hydroxylated steroids and homologs of 16α-hydroxy-DHEA were also found. This study shows that all enzymatic steps used by cholesterol in the DHEA synthetic pathway are also functional for 7DHC and 8DHC.

Original languageEnglish (US)
Pages (from-to)481-490
Number of pages10
JournalSteroids
Volume64
Issue number7
DOIs
StatePublished - Jul 1999

Fingerprint

Smith-Lemli-Opitz Syndrome
Steroids
Metabolites
Dehydroepiandrosterone
Urine
Mass spectrometry
Cholesterol
7-dehydrocholesterol reductase
Gas chromatography
Gas Chromatography-Mass Spectrometry
Mass Spectrometry

Keywords

  • 7-Dehydrocholesterol
  • 7-Dehydrocholesterol reductase
  • Gas chromatography/mass spectrometry
  • Neonatal steroids
  • Pregnadienes
  • Smith-Lemli-Opitz syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Neonatal urinary steroids in Smith-Lemli-Opitz syndrome associated with 7-dehydrocholesterol reductase deficiency. / Shackleton, Cedric H L; Roitman, Esther; Kelley, Richard.

In: Steroids, Vol. 64, No. 7, 07.1999, p. 481-490.

Research output: Contribution to journalArticle

Shackleton, Cedric H L ; Roitman, Esther ; Kelley, Richard. / Neonatal urinary steroids in Smith-Lemli-Opitz syndrome associated with 7-dehydrocholesterol reductase deficiency. In: Steroids. 1999 ; Vol. 64, No. 7. pp. 481-490.
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