Fetal Smith-Lemli-Opitz syndrome can be detected accurately and reliably by measuring amniotic fluid dehydrocholesterols.
The Smith-Lemli-Opitz syndrome, characterized by limb, face and organ abnormalities, and mental retardation, is caused by an inherited block in the step of cholesterol biosynthesis in which the delta 7 double bond of 7-dehydrocholesterol is reduced. It is diagnosed by the presence of markedly elevated levels of 7-dehydrocholesterol and 8-dehydrocholesterol in plasma and tissue. We measured amniotic fluid sterols in 15 pregnancies in 13 women who had previously carried an affected fetus. Cholesterol, 7-dehydrocholesterol and 8-dehydrocholesterol concentrations averaged 18 +/- 3, 9.8 +/- 2.9 and 5.0 +/- 1.7 micrograms/ml, respectively, in seven pregnancies with an affected fetus or child. In contrast, these levels were 19 +/- 3, 0.05 +/- 0.01 and < 0.005 micrograms/ml, respectively, in eight increased-risk pregnancies with normal outcomes and 16 +/- 2, 0.07 +/- 0.01 and < 0.005 micrograms/ml in normal controls. 7-dehydrocholesterol concentrations, 2.2-26 and 0.05-0.10 micrograms/ml in pregnancies with an affected and unaffected fetus, respectively, did not overlap. Thus, abnormally elevated amniotic fluid dehydrocholesterol concentrations are an accurate predictor of fetal Smith-Lemli-Opitz syndrome. A false-positive or a false-negative result is highly unlikely.
Department of Veterans Affairs Medical Center, East Orange, NJ 07018, USA. tintgs@umdnj.edu
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D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000737:chemistry*; D002775:Cholestadienols / Q000032:analysis*; D002784:Cholesterol / Q000032:analysis; D003684:Dehydrocholesterols / Q000032:analysis*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005865:Gestational Age; D006801:Humans; D011247:Pregnancy; D011256:Pregnancy Outcome; D012016:Reference Values; D019082:Smith-Lemli-Opitz Syndrome / Q000175:diagnosis*
D002775:Cholestadienols; D003684:Dehydrocholesterols; C026359:cholesta-5,8-dien-3 beta-ol; D002784:Cholesterol; C016705:7-dehydrocholesterol