Dehydro-oestriol and dehydropregnanetriol are candidate analytes for prenatal diagnosis of Smith-Lemli-Opitz syndrome

Gas chromatographic/mass spectrometric (GC/MS) analysis of maternal urine and serum steroids from 13 pregnancies at 25% risk for Smith-Lemli-Opitz syndrome (SLOS) was undertaken. All patients were between 12 and 31 weeks' gestational age From dehydrocholesterol/cholesterol ratios determined in amniotic fluid and chorionic villus cells, five patients were shown to carry SLOS affected fetuses and eight patients were negative for the condition. Because it had previously been shown that dehydro-oestriol and dehydropregnanetriol were novel steroids produced in SLOS, these compounds were measured in the serum and urine samples of the 13 mothers. All five urine samples from SLOS affected pregnancies had high levels of both dehydrosteroid metabolites, which were below the detection limit in the non-affected pregnancies. The ratios of dehydro--oestriol/oestriol (DHE 3 /E 3 ) were between 0.073 and 1.42 for the affected patients and less than 0.01 for unaffected patients. Corresponding values for dehydropregnanetriol/pregnanetriol (DHPT/PT) were 0.037 1.02 for affected and less than 0.01 for unaffected. In the positive serum sample available for analysis, the DHE 3 /E 3 ratio was 0.20 [unaffected (n=5), <0.014]. It is proposed that the measurement of DHE 3 and DHPT in maternal urine and serum may allow non-invasive antenatal diagnosis of SLOS.