Congenital adrenal hyperplasia: molecular genetics and alternative approaches to treatment

Crit Rev Clin Lab Sci. 1999 Aug;36(4):329-63. doi: 10.1080/10408369991239222.


Several autosomal recessive disorders affecting the adrenal cortex and its development and leading to defective cortisol biosynthesis are known under the collective term "congenital adrenal hyperplasia" (CAH). Over the last two decades, the genes causing most of these disorders have been identified and molecular genetics may supplement their clinical and biochemical diagnosis. In addition, new treatments have emerged; although gene therapy has yet to be applied in humans, studies are ongoing in gene transfer in adrenocortical cell lines and animal models. In this review, after a brief introduction on the developmental biology and biochemistry of the adrenal cortex and its enzymes, we will list the new developments in the genetics and treatment of diseases causing CAH, starting with the most recent findings. This order happens to follow adrenal steroidogenesis from the mitochondrial entry of cholesterol to cortisol synthesis; it is unlike other presentations of CAH syndromes that start with the most frequently seen syndromes, because the latter were also the first to be investigated at the genetic level and have been extensively reviewed elsewhere. We will start with the latest syndrome to be molecularly investigated, congenital lipoid adrenal hyperplasia (CLAH), which is caused by mutations in the gene coding for the steroidogenic acute regulatory (StAR) protein. We will then present new developments in the genetics of 3-beta-hydroxysteroid dehydrogenase (3 beta HSD), 17 hydroxylase and 17,20-lyase (P450c17), 11 hydroxylase (P450c11 beta), and 21 hydroxylase (P450c21) deficiencies. Alternative treatment approaches and gene therapy experiments are reviewed collectively in the last section, because they are still in their infantile stages.

Publication types

  • Review

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / deficiency
  • 3-Hydroxysteroid Dehydrogenases / genetics
  • Adrenal Cortex / embryology
  • Adrenal Cortex / metabolism
  • Adrenal Hyperplasia, Congenital / genetics*
  • Adrenal Hyperplasia, Congenital / therapy*
  • Female
  • Genitalia / embryology
  • Humans
  • Male


  • 3-Hydroxysteroid Dehydrogenases