Disorders of Cholesterol Biosynthesis

Cholesterol has several essential functions in cell physiology. In addition to being a major component of cellular membranes, cholesterol serves as the precursor of bile acids and steroid hormones and plays an important role in embryonic morphogenesis. For many years, mevalonate kinase deficiency (MKD) was the only known genetic disorder of the cholesterol biosynthesis pathway (Hoffmann et al. Pediatrics 91:915–921, 1993). However, the discovery in 1993 of increased levels of 7-dehydrocholesterol (7DHC) and hypocholesterolemia in patients with Smith-Lemli-Opitz syndrome (SLOS) (Irons et al. Lancet 341:1414, 1993) heralded the emergence of a new group of metabolic disorders—inborn errors of cholesterol biosynthesis. The discovery of the biochemical bases of these rare genetic disorders has not only provided biochemical methods for their diagnosis but also allowed the delineation of the broad spectrum of their clinical and biochemical phenotypes.