Midgestational maternal urine steroid markers of fetal Smith-Lemli- Opitz (SLO) syndrome (7-dehydrocholesterol 7-reductase deficiency)

Cedric H L Shackleton, Esther Roitman, Lisa Kratz, Richard I. Kelley

Research output: Contribution to journalArticle

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome associated with 7-dehydrocholesterol (7DHC) 7-reductase deficiency. Although SLOS can be detected in an affected fetus before midpregnancy by measurement of 7DHC levels in amniotic fluid or chorionic villus cells, a noninvasive, more routine method is needed. Accordingly, this study was instigated to search for specific steroids in maternal urine in an affected pregnancy that reflect the 7-reductase deficiency of the fetus, ie, steroids retaining 7,8- unsaturation. Steroids were characterized by gas chromatography/mass spectrometry after urinary extraction, conjugate separation, and derivatization. Most steroids in maternal urine from a patient carrying a SLOS fetus were identified as progesterone metabolites, and these were entirely conventional, showing no evidence of additional unsaturation. Unsaturated homologues of the cortisol metabolites were also not detected. However, unsaturated homologues of pregnane-3,16,20-triols and pregnane- 3,17,20-triol were found. Most likely, these are 7,8-unsaturated homologues, but 8,9-unsaturation is also possible because of the known activity of Δ7- Δ8-isomerase on 7DHC, which results in 8DHC being a prominent sterol in SLOS. Among these novel human steroids, the following were provisionally characterized: 5β-pregn-7(or 8)-ene3α, 17α,20α-triol, 5β-pregn-7(or 8)- ene-3α, 16α,20α-triol, and 5α-pregn-7(or 8)-ene-3,16α,20α-triol. Confirmation of the position of unsaturation will require steroid synthesis. These novel steroids are not present in normal pregnancy urine and, therefore, are valuable for prenatal diagnosis of SLOS. In addition, separate studies have shown that 5β-pregn-7(or 8)-ene-3α,17α,20α-triol is present in urine of children and adults with SLOS, and so is a useful analyte for confirmation of the disorder throughout life.

Original languageEnglish (US)
Pages (from-to)446-452
Number of pages7
JournalSteroids
Volume64
Issue number7
DOIs
StatePublished - Jul 1999

Fingerprint

Smith-Lemli-Opitz Syndrome
Oxidoreductases
Steroids
Mothers
Urine
Pregnanes
Fetus
Metabolites
Chorionic Villi
Pregnancy
Isomerases
Sterols
Amniotic Fluid
7-dehydrocholesterol
Prenatal Diagnosis
Gas chromatography
Gas Chromatography-Mass Spectrometry
Mass spectrometry
Progesterone
Hydrocortisone

Keywords

  • Δ-Δ- Pregnenetriols
  • Gas chromatography/mass spectrometry
  • Pregnancy urine steroids
  • Smith-Lemli-Opitz syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Midgestational maternal urine steroid markers of fetal Smith-Lemli- Opitz (SLO) syndrome (7-dehydrocholesterol 7-reductase deficiency). / Shackleton, Cedric H L; Roitman, Esther; Kratz, Lisa; Kelley, Richard I.

In: Steroids, Vol. 64, No. 7, 07.1999, p. 446-452.

Research output: Contribution to journalArticle

Shackleton, Cedric H L ; Roitman, Esther ; Kratz, Lisa ; Kelley, Richard I. / Midgestational maternal urine steroid markers of fetal Smith-Lemli- Opitz (SLO) syndrome (7-dehydrocholesterol 7-reductase deficiency). In: Steroids. 1999 ; Vol. 64, No. 7. pp. 446-452.
@article{300c4681ed6d40daad13cb2cc060ff4e,
title = "Midgestational maternal urine steroid markers of fetal Smith-Lemli- Opitz (SLO) syndrome (7-dehydrocholesterol 7-reductase deficiency)",
abstract = "Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome associated with 7-dehydrocholesterol (7DHC) 7-reductase deficiency. Although SLOS can be detected in an affected fetus before midpregnancy by measurement of 7DHC levels in amniotic fluid or chorionic villus cells, a noninvasive, more routine method is needed. Accordingly, this study was instigated to search for specific steroids in maternal urine in an affected pregnancy that reflect the 7-reductase deficiency of the fetus, ie, steroids retaining 7,8- unsaturation. Steroids were characterized by gas chromatography/mass spectrometry after urinary extraction, conjugate separation, and derivatization. Most steroids in maternal urine from a patient carrying a SLOS fetus were identified as progesterone metabolites, and these were entirely conventional, showing no evidence of additional unsaturation. Unsaturated homologues of the cortisol metabolites were also not detected. However, unsaturated homologues of pregnane-3,16,20-triols and pregnane- 3,17,20-triol were found. Most likely, these are 7,8-unsaturated homologues, but 8,9-unsaturation is also possible because of the known activity of Δ7- Δ8-isomerase on 7DHC, which results in 8DHC being a prominent sterol in SLOS. Among these novel human steroids, the following were provisionally characterized: 5β-pregn-7(or 8)-ene3α, 17α,20α-triol, 5β-pregn-7(or 8)- ene-3α, 16α,20α-triol, and 5α-pregn-7(or 8)-ene-3,16α,20α-triol. Confirmation of the position of unsaturation will require steroid synthesis. These novel steroids are not present in normal pregnancy urine and, therefore, are valuable for prenatal diagnosis of SLOS. In addition, separate studies have shown that 5β-pregn-7(or 8)-ene-3α,17α,20α-triol is present in urine of children and adults with SLOS, and so is a useful analyte for confirmation of the disorder throughout life.",
keywords = "Δ-Δ- Pregnenetriols, Gas chromatography/mass spectrometry, Pregnancy urine steroids, Smith-Lemli-Opitz syndrome",
author = "Shackleton, {Cedric H L} and Esther Roitman and Lisa Kratz and Kelley, {Richard I.}",
year = "1999",
month = "7",
doi = "10.1016/S0039-128X(99)00026-4",
language = "English (US)",
volume = "64",
pages = "446--452",
journal = "Steroids",
issn = "0039-128X",
publisher = "Elsevier Inc.",
number = "7",

}

TY - JOUR

T1 - Midgestational maternal urine steroid markers of fetal Smith-Lemli- Opitz (SLO) syndrome (7-dehydrocholesterol 7-reductase deficiency)

AU - Shackleton, Cedric H L

AU - Roitman, Esther

AU - Kratz, Lisa

AU - Kelley, Richard I.

PY - 1999/7

Y1 - 1999/7

N2 - Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome associated with 7-dehydrocholesterol (7DHC) 7-reductase deficiency. Although SLOS can be detected in an affected fetus before midpregnancy by measurement of 7DHC levels in amniotic fluid or chorionic villus cells, a noninvasive, more routine method is needed. Accordingly, this study was instigated to search for specific steroids in maternal urine in an affected pregnancy that reflect the 7-reductase deficiency of the fetus, ie, steroids retaining 7,8- unsaturation. Steroids were characterized by gas chromatography/mass spectrometry after urinary extraction, conjugate separation, and derivatization. Most steroids in maternal urine from a patient carrying a SLOS fetus were identified as progesterone metabolites, and these were entirely conventional, showing no evidence of additional unsaturation. Unsaturated homologues of the cortisol metabolites were also not detected. However, unsaturated homologues of pregnane-3,16,20-triols and pregnane- 3,17,20-triol were found. Most likely, these are 7,8-unsaturated homologues, but 8,9-unsaturation is also possible because of the known activity of Δ7- Δ8-isomerase on 7DHC, which results in 8DHC being a prominent sterol in SLOS. Among these novel human steroids, the following were provisionally characterized: 5β-pregn-7(or 8)-ene3α, 17α,20α-triol, 5β-pregn-7(or 8)- ene-3α, 16α,20α-triol, and 5α-pregn-7(or 8)-ene-3,16α,20α-triol. Confirmation of the position of unsaturation will require steroid synthesis. These novel steroids are not present in normal pregnancy urine and, therefore, are valuable for prenatal diagnosis of SLOS. In addition, separate studies have shown that 5β-pregn-7(or 8)-ene-3α,17α,20α-triol is present in urine of children and adults with SLOS, and so is a useful analyte for confirmation of the disorder throughout life.

AB - Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome associated with 7-dehydrocholesterol (7DHC) 7-reductase deficiency. Although SLOS can be detected in an affected fetus before midpregnancy by measurement of 7DHC levels in amniotic fluid or chorionic villus cells, a noninvasive, more routine method is needed. Accordingly, this study was instigated to search for specific steroids in maternal urine in an affected pregnancy that reflect the 7-reductase deficiency of the fetus, ie, steroids retaining 7,8- unsaturation. Steroids were characterized by gas chromatography/mass spectrometry after urinary extraction, conjugate separation, and derivatization. Most steroids in maternal urine from a patient carrying a SLOS fetus were identified as progesterone metabolites, and these were entirely conventional, showing no evidence of additional unsaturation. Unsaturated homologues of the cortisol metabolites were also not detected. However, unsaturated homologues of pregnane-3,16,20-triols and pregnane- 3,17,20-triol were found. Most likely, these are 7,8-unsaturated homologues, but 8,9-unsaturation is also possible because of the known activity of Δ7- Δ8-isomerase on 7DHC, which results in 8DHC being a prominent sterol in SLOS. Among these novel human steroids, the following were provisionally characterized: 5β-pregn-7(or 8)-ene3α, 17α,20α-triol, 5β-pregn-7(or 8)- ene-3α, 16α,20α-triol, and 5α-pregn-7(or 8)-ene-3,16α,20α-triol. Confirmation of the position of unsaturation will require steroid synthesis. These novel steroids are not present in normal pregnancy urine and, therefore, are valuable for prenatal diagnosis of SLOS. In addition, separate studies have shown that 5β-pregn-7(or 8)-ene-3α,17α,20α-triol is present in urine of children and adults with SLOS, and so is a useful analyte for confirmation of the disorder throughout life.

KW - Δ-Δ- Pregnenetriols

KW - Gas chromatography/mass spectrometry

KW - Pregnancy urine steroids

KW - Smith-Lemli-Opitz syndrome

UR - http://www.scopus.com/inward/record.url?scp=0032801752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032801752&partnerID=8YFLogxK

U2 - 10.1016/S0039-128X(99)00026-4

DO - 10.1016/S0039-128X(99)00026-4

M3 - Article

C2 - 10443900

AN - SCOPUS:0032801752

VL - 64

SP - 446

EP - 452

JO - Steroids

JF - Steroids

SN - 0039-128X

IS - 7

ER -