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Cited by 234Metabolism and Genetic DisordersCholesterol and Lipid MetabolismLysosomal Storage Disorders Research

Diagnosis of Smith-Lemli-Opitz syndrome by gas chromatography/mass spectrometry of 7-dehydrocholesterol in plasma, amniotic fluid and cultured skin fibroblasts

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Kelley, Richard I.·1995·Clinica Chimica Acta
DOI 10.1016/0009-8981(95)06038-4
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Abstract

A method is described for quantification of 7-dehydrocholesterol (7DHC) and other neutral sterols by gas chromatography/mass spectrometry for diagnosis of Smith-Lemli-Opitz syndrome, an apparent primary defect of cholesterol biosynthesis associated with low plasma levels of cholesterol and high levels of its precursor, 7DHC. Results are summarized for specimens from normal controls and from 40 patients with Smith-Lemli-Opitz syndrome (SLOS). Whereas the concentration of 7DHC (as a combined peak of 7DHC and iso-7DHC) in normal infant plasma was found to be 0.10 +/- 0.05 (S.D.) microgram/ml, the level in patients with SLOS ranged from 2.7 to 470 micrograms/ml, or from 10 to more than 2000 times the upper limit of normal. Patients with milder type I SLOS as well as those with the more severe type II SLOS were found to have the same sterol abnormality. Although most infants with SLOS had plasma cholesterol levels lower than 400 micrograms/ml (40 mg/dl), several older children with only mildly increased levels of 7DHC had normal plasma cholesterol levels. Diagnostically useful, comparably increased levels of 7DHC were found in amniotic fluid and cultured skin fibroblasts from patients with SLOS. More mildly increased levels of 7DHC were also found in both plasma and cultured skin fibroblasts of SLOS heterozygotes. The method described uses capillary columns and GC/MS instrumentation available in most biochemical genetics laboratories and should prove useful not only for diagnosis and prenatal diagnosis of Smith-Lemli-Opitz syndrome, but also for identification of other possible inborn errors of sterol biosynthesis.

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  • The SLOS anatomical severity score and gross neurologic pathology inversely correlate with cholesterol and the ratio of 7DHC + 8DHC to cholesterol.

    “The SLOS anatomical severity score and gross neurologic pathology inversely correlate with cholesterol and the ratio of 7DHC + 8-dehydrocholesterol (8DHC) to cholesterol [48, 49];”

    From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [48]

    Section 3.3 reports a reciprocal relationship between 7DHC and cholesterol levels in older patients, but not a correlation of either measure with anatomical severity or neurologic pathology. The Abstract notes sterol abnormalities in both milder and more severe SLOS; the passages found do not assess an anatomical severity score, gross neurologic pathology, or the claimed (7DHC + 8DHC)-to-cholesterol ratio. (LLM, conf=0.74)

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Cites

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Research works printed but not linked: 2

  1. Smith DW, Lemli L, Opitz JM. A newly recognized syndrome of multiple congenital abnormalities. J Pediatr 1964;64:210-217.
  2. Penchaszadeh VB. The nosology of the Smith-Lemli-Opitz Syndrome. Am J Med Genet 1987;28:719-721.

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Authors
Kelley, R. I.
Affiliations
Johns Hopkins University (US)
Corresponding author
Kelley, Richard I.
ORCID
Kelley, Richard I.
Venue
Clinica Chimica Acta
Publisher
Elsevier BV
Published
1995-04
Volume
236
Issue
1
Pages
45-58
ISSN
0009-8981 (ISSN-L)
DOI
10.1016/0009-8981(95)06038-4
OpenAlex
W2038396364
Cited by
234
References
16
Citations by year
2025: 6 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 11 · 2014: 8 · 2013: 10 · 2012: 9
FWCI
6.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinica Chimica Acta (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Johns Hopkins University
  • National Institutes of Health
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD07107, HD24061, HD-10981, P30HD024061, P01HD010981)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
Smith-Lemli-Opitz syndrome, 7-dehydrocholesterol, cholesterol biosynthesis, neutral sterols, serum cholesterol, amniotic fluid, cultured skin fibroblasts, prenatal diagnosis, heterozygotes
MeSH terms
Abnormalities, Multiple, Adolescent, Adult, Amniotic Fluid, Cells, Cultured, Child, Child, Preschool, Cholesterol, Dehydrocholesterols, Fibroblasts, Humans, Infant, Lipid Metabolism, Inborn Errors, Gas Chromatography-Mass Spectrometry, Skin, Sterols, Molecular Structure

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