Congenital Lipoid Adrenal Hyperplasia (CLAH) or Lipoid CAH


Congenital lipoid adrenal hyperplasia (CLAH; Steroid 20-22 desmolase deficiency; lipoid CAH) is caused by a defect in the CYP11A1 gene which codes for mitochondrial cholesterol side-chain cleavage enzyme. Cholesterol side-chain cleavage enzyme convertes cholesterol to pregnenolone in adrenal cortisol synthesis of all steroid hormones. A defect in this enzyme results in in impaired synthesis of all three categories of adrenal steroids (cortisol, mineralocorticoids, sex steroids) and high levels of adrenocorticotropic hormone (ACTH). Symptoms include poor feeding, vomiting, dehydration, hypotension, hyponatremia, hyperkalemia, hypoglycemia, hyperpigmentation. Sex steroid deficiency can result in ambiguous genitalia. Patients need the mineral replacement and extra glucocorticoid. XX female patients can use estrogen replacement at or after puberty. For XY patients, the testes are uniformly nonfunctional and they are undescended, are removed when the diagnosis is made due to the risk of cancer development in these tissues.

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References

  1. Uniprot: P05108
  2. Wikipedia: Lipoid congenital adrenal hyperplasia
  3. Bose HS, Sugawara T, Strauss JF 3rd, Miller WL: The pathophysiology and genetics of congenital lipoid adrenal hyperplasia. International Congenital Lipoid Adrenal Hyperplasia Consortium. N Engl J Med. 1996 Dec 19;335(25):1870-8. Pubmed
  4. Degenhart HJ, Visser HK, Boon H, O’Doherty NJ: Evidence for deficient 20 -cholesterol-hydroxylase activity in adrenal tissue of a patient with lipoid adrenal hyperplasia. Acta Endocrinol (Copenh). 1972 Nov;71(3):512-8. Pubmed
  5. Fox RR, Crary DD: Genetics and pathology of hereditary adrenal hyperplasia in the rabbit: a model for congenital lipoid adrenal hyperplasia. J Hered. 1978 Jul-Aug;69(4):251-4. Pubmed
  6. Hauffa BP, Miller WL, Grumbach MM, Conte FA, Kaplan SL: Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20, 22-desmolase) in a patient treated for 18 years. Clin Endocrinol (Oxf). 1985 Nov;23(5):481-93. Pubmed