Pitfalls in measuring plasma cholesterol in the Smith-Lemli-Opitz syndrome

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 43; no. 1; pp. 129 - 133
• Main Authors: JIRA, P. E, DE JONG, J. G. N, JANSSEN-ZIJLSTRA, F. S. M, WENDEL, U, WEVERS, R. A
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Washington, DC American Association for Clinical Chemistry 1997
• Subjects: Adult; Biological and medical sciences; Child; Cholestadienols - blood; Cholesterol - blood; Cholesterol Oxidase; Chromatography, Gas; Dehydrocholesterols - blood; Disorders of blood lipids. Hyperlipoproteinemia; False Positive Reactions; Humans; Infant; Infant, Newborn; Medical sciences; Metabolic diseases; Reference Values; Smith-Lemli-Opitz Syndrome - blood; Smith-Lemli-Opitz Syndrome - diagnosis; Human; Biological fluid; Metabolic diseases; Exploration; Lipids; Syndrome; Cholesterol; Blood plasma; Gas chromatography; Investigation method; Laboratory investigations; Smith Lemli Opitz dwarfism; Clinical biology; Morphological change; Dyslipemia; Quantitative analysis
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/43.1.129

Correct quantitative results for plasma cholesterol, 7-dehydrocholesterol (7-DHC), and 8-dehydrocholesterol (8-DHC) are invaluable for making the correct diagnosis in patients with the Smith-Lemli-Opitz syndrome (SLO) and for biochemical monitoring of these patients during therapy. The enzymatic method for cholesterol measurement based on cholesterol oxidase gives falsely high values for plasma cholesterol in samples from patients with SLO. Both 7-DHC and 8-DHC contribute substantially to the test result, given that they are accepted substrates of cholesterol oxidase. All cholesterol methods making use of this enzyme are expected to give unreliable results with plasma samples from SLO patients. Cholesterol values found with these methods may be low-normal in individual cases with SLO. Therefore, other techniques for measuring cholesterol, 7-DHC, and 8-DHC, e.g., gas chromatography, should be used for diagnosing these patients and for follow-up during therapy. However, a normal value for plasma cholesterol, as obtained by gas chromatography, does not exclude SLO. The diagnosis should always be confirmed or excluded by testing for the presence of high concentrations of 7-DHC and 8-DHC in plasma. We found that one patient with a severe form of the disease had a plasma cholesterol concentration of 20 micromol/L-to our knowledge, the lowest value ever recorded in a human being.