Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia due to 21-hydroxylase Deficiency


Adrenal hyperplasia type 3, also called Congenital adrenal hyperplasia due to 21-hydroxylase deficiency, is caused by a defect in the CYP21A2 gene which codes for Steroid 21-hydroxylase (21-hydroxylase). Steroid 21-hydroxylase catalyzes hydroxylation of 17-hydroxyprogesterone to 11-deoxycortisol in the glucocorticoid pathway from pregnenolone to cortisol. It also catalyzes hydroxylation of progesterone to 11-deoxycorticosterone (DOC) in the mineralocorticoid pathway on its way from pregnenolone to aldosterone. A defect in this enzyme results in accumulation of 17-Hydroxyprogesterone, progesterone and 17a-Hydroxypregnenolone, androstenedione, and testosterone; decreased levels of cortexolone, deoxycorticosterone, aldosterone and cortisol. Symptoms include salt-wasting crises in infancy due to the lack of aldosterone, like spitting, poor weight gain, vomiting, severe dehydration, and circulatory collapse. The high level of testosterone results in virilization and genital ambiguity of female infants.

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References

  1. Uniprot: P08686
  2. eMedicine: Article 923876-diagnosis
  3. Wikipedia: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
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  5. Araujo RS, Mendonca BB, Barbosa AS, Lin CJ, Marcondes JA, Billerbeck AE, Bachega TA: Microconversion between CYP21A2 and CYP21A1P promoter regions causes the nonclassical form of 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2007 Oct;92(10):4028-34. Epub 2007 Jul 31. Pubmed
  6. Bachega TA, Billerbeck AE, Madureira G, Marcondes JA, Longui CA, Leite MV, Arnhold IJ, Mendonca BB: Molecular genotyping in Brazilian patients with the classical and nonclassical forms of 21-hydroxylase deficiency. J Clin Endocrinol Metab. 1998 Dec;83(12):4416-9. Pubmed
  7. BONGIOVANNI AM, ROOT AW: The adrenogenital syndrome. N Engl J Med. 1963 Jun 6;268:1283-9 contd. Pubmed
  8. Charmandari E, Hindmarsh PC, Johnston A, Brook CG: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: alterations in cortisol pharmacokinetics at puberty. J Clin Endocrinol Metab. 2001 Jun;86(6):2701-8. Pubmed