Disorders of Sterol Biosynthesis

As a major component of the cell membrane of most eukaryotic cells, cholesterol assumes crucial roles in myelination of the central and peripheral nervous systems, in the synthesis of bile acids, steroids, and vitamin D, in sterol signaling, and in embryonic development. Inborn errors of cholesterol biosynthesis comprise a heterogeneous group of disorders characterized by developmental delays, increased tissue levels of specific sterol intermediates, and complex malformations involving many organ systems. Here we present the basics of cholesterol biosynthesis and review the clinical phenotype, biochemistry, molecular pathogenesis, and management of the 8 known errors of sterol metabolism in humans: Antley-Bixtler syndrome, Greenberg dysplasia, X-linked dominant congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome), X-linked dominant chondrodysplasia punctata (Conradi-Hünermann syndrome; CDPX2), lathosterolosis, Smith-Lemli-Opitz syndrome, desmosterolosis, and methyl sterol oxidase (SC4MOL) deficiency.