The enzymatic steps impaired in these inborn errors of metabolism include mevolonate kinase (mevalonic aciduria as well as hyperimmunoglobulinemia D and periodic fever syndrome), squalene synthase (Ss-/- mouse), 3beta-hydroxysteroid Delta14-reductase (hydrops-ectopic calcification-moth-eaten skeletal dysplasia), 3beta-hydroxysteroid dehydrogenase (CHILD syndrome, bare patches mouse, and striated mouse), 3beta-hydroxysteroid Delta8,Delta7-isomerase (X-linked dominant chondrodysplasia punctata type 2, CHILD syndrome, and tattered mouse), 3beta-hydroxysteroid Delta24-reductase (desmosterolosis) and 3beta-hydroxysteroid Delta7-reductase (RSH/Smith-Lemli-Opitz syndrome and Dhcr7-/- mouse).
To investigate in vivo regulation of the cholesterol biosynthetic pathway in SLOS, we measured hepatic microsomal sterol concentrations and activities of several key enzymes in the pathway, including HMG-CoA synthase, HMG-CoA reductase, squalene synthase and 7-dehydrocholesterol delta7-reductase in liver specimens from a patient with SLOS and 11 controls.