ABSTRACT
Mevalonic aciduria was discovered in 1986, the first inborn error in the biosynthesis of cholesterol and nonsterol isoprenoid compounds. A missense mutation was identified in the index patient with mevalonic aciduria, an A-to-C change at nucleotide 902 causing a change of asparagine 301 to threonine. Mevalonic acid clearance by the kidney is very efficient and it appears to involve active renal tubular secretion. Mevalonic acid occupies a unique place in intermediary metabolism. The pathway is regulated via feedback inhibition by cholesterol of the synthesis of mevalonic acid at the 3-hydroxy-3-methylglutaryl-coenzyme A reductase step. The pregnancy was terminated, and the diagnosis confirmed by assay of the enzyme in fetal tissues. The initial enzymes in the nonsterol branches of the pathway have a very high affinity for farnesylpyrophosphate. The enzyme is also active in freshly isolated lymphocytes and defective activity has been documented in lymphocytes of patients.
