ldentif ication of 8-de hydroc holesterol (c holesta-5,8-d ien-30 -01) i n patients with S m it h- Lem I i-0 p i t z syndrome

Cholesta-5,8-dien-3fl-o1 (8-dehydrocholesterol) and cholesta-5,7-dien-3~-ol(7-dehydrocholesterol) were isolated from the fecal neutral sterol fraction from homozygotes with Smith- Lemli-Opitz syndrome. The structures of the sterols were con- clusively established from their mass spectra and 1H and *3C nuclear magnetic resonance spectra. It is probable that 8-dehydro- cholesterol arises from 7-dehydrocholesterol and is not a direct precursor of cholesterol.-Batta, A. K., G. S. Tint, S. Shefer, D. Abuelo, and G. Salen. Identification of 8-dehydrocholesterol (cholesta-5,8-dien-3@-ol) in patients with Smith-Lemli-Opitz syndrome. J. Lipid Res. 1995. 36: 705-713. Smith-Lemli-Opitz syndrome is a devastating, often fa- tal autosomal recessive disorder characterized by a large number of birth defects affecting nearly every organ sys- tem (1-6). The most discernible abnormalities are a set of distinctive dysmorphic facial features: microcephaly, micro- gnathia, cataracts, ptosis, wide nasal bridge with an- teverted nares, and low set posteriorly rotated ears. Limb abnormalities are also common with syndactyly of the se- cond and third toe noted in at least 75% of cases and polydactyly seen in 20-25% of patients. The most se- verely affected patients exhibit genital disorders, espe- cially cryptorchidism, hypospadias, and microphalus and often die prematurely. Also reported are widespread defects in many endocrine glands (complete absence of lipid in adrenal cortex), liver, kidneys and urinary system, heart, lungs, and skeleton. These children are mentally retarded and they often show severe failure to thrive and frequently require a gastrostomy feeding tube. The condi- tion is estimated to be the third most common auto- somal recessive disorder among North American Cauca- sians after cystic fibrosis and phenylketonuria; and its prevalence is approximately 1 out of 20,000 births (6). We have recently described a severe abnormality in cholesterol biosynthesis in five homozygotes with this syn- drome in which we found extremely low plasma cholesterol levels associated with the accumulation of the cholesterol precursor, cholesta-5,7-dien-3P-o1 (7-dehydrocholesterol) as well as an unidentified isomeric dehydrosterol (7-10). In this report, we describe the unequivocal characteriza- tion of this sterol as cholesta-5,8-dien-3/3-01 (8-dehydro- cholesterol) (Fig. 1) based on its 1H and 1% nuclear mag- netic resonance (NMR) spectral studies.