Recognition of Smith Lemli Opitz syndrome by characteristic steroids
JW Honour, I Phillips & E Conway
Congenital adrenal hyperplasia(CAH) and other disorders of adrenal steroid synthesis compromise synthesis of cortisol and aldosterone. Deficiency of 7-dehydrocholesterol-7-ene-reductase (DHCR7) in the Smith Lemli Opitz syndrome (SLOS) also affects cholesterol synthesis. New-born infants have dysmorphic facial features, microcephaly, second and third toe syndactyly and genital malformations. Later there is mental retardation and problems with cardiac and intestinal function through lack of bile acid production. The disorder is usually located by analysis of cholesterol and 7-dehydrocholesterol in blood. In two cases of new-born infants with ambiguous genitalia urine was sent to the SAS laboratory for steroid profile analysis. Cortisol metabolites were absent and no metabolites of precursor steroids were found to support CAH due to common defects of cortisol synthesis. Several steroids on mass spectrometry showed spectral patterns suggestive of unsaturated products of steroids often seen in new-born urine. 7-dehydro metabolites of 16-hydroxy-DHA, 16 hydroxypregnenolone and pregnanetriol were detected in a steroid pattern that will now be useable for SLOS recognition. These data indicate that adrenal mitochondria and some cytoplasmic enzymes can process 7-dehydrocholesterol. 7-dehydro steroids may also be detected in pregnancy, which would be recognisable through detection of 7-dehydro steroids in maternal urine.