Cholesterol metabolism in the RSH/Smith-Lemli-Opitz syndrome: summary of an NICHD conference

During the evolution of multicellularity and attendant processes of development, cholesterol played a key role in the formation of the plasma membrane and outer mitochondrial membrane of every cell in the organism. Later functions include pivotal involvement in steroid, bile acid, and vitamin D metabolism and myelination of the nervous system. In the CNS myelination does not begin until the third trimester, and subcortical myelination not until after birth. The cholesterol of the cell membrane of the ovum is maternally derived. It is not known when the zygote begins making its own cholesterol during morphogenesis and histogenesis, but it must occur early to keep up with the dramatic rate of cell division in the embryo. Thus, it is a startling surprise that human embryos and fetuses apparently able to synthesize little cholesterol (because of a presumed defect of the delta 5,7-sterol, delta 7-reductase that converts 7-dehydrocholesterol (7-DHC) into cholesterol) frequently live to term and, rarely, may be so mildly affected as to attend school with only mild MR. The discovery by G. Stephen Tint and his co-workers of the apparent 7-DHC reductase deficiency makes the RSH (Smith-Lemli-Opitz) syndrome the first true metabolic malfor...Continue Reading