TY - CHAP M1 - Book, Section TI - Smith-Lemli-Opitz Syndrome A1 - Kelley, Richard I. A1 - Hennekam, Raoul C. M. A2 - Valle, David L. A2 - Antonarakis, Stylianos A2 - Ballabio, Andrea A2 - Beaudet, Arthur L. A2 - Mitchell, Grant A. Y1 - 2019 N1 - 10.1036/ommbid.289 T2 - The Online Metabolic and Molecular Bases of Inherited Disease AB - Although cholesterol metabolism has been one of the most intensely studied metabolic pathways in humans, for many years the only known primary defect of the cholesterol biosynthetic pathway was mevalonic aciduria, a rare autosomal recessive deficiency of mevalonate kinase associated with developmental delays, craniofacial dysmorphism, and a variety of systemic and metabolic abnormalities (Branched Chain Organic Acidurias). However, in 1993, a second defect of cholesterol synthesis, a deficiency of 7-dehydrocholesterol reductase (DHCR7), was found to be the apparent cause of the RSH/Smith-Lemli-Opitz syndrome (SLOS), a relatively common autosomal-recessive multiple-malformation syndrome. Patients with both mild and severe forms of SLOS had markedly increased levels of 7-dehydrocholesterol (7DHC) and decreased levels of cholesterol. The finding 5 years later of disabling mutations in the DHCR7 gene in patients with SLOS confirmed SLOS as the second defect of cholesterol biosynthesis and the first affecting sterol metabolism per se. SN - PB - McGraw-Hill Education CY - New York, NY M3 - doi: 10.1036/ommbid.289 Y2 - 2024/03/28 UR - ommbid.mhmedical.com/content.aspx?aid=1184072392 ER -