Molecular pathogenesis of lipoid adrenal hyperplasia and adrenal hypoplasia congenita.

Abstract

Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH in which the synthesis of all gonadal and adrenal cortical steroids is markedly impaired. Lipoid CAH may be caused by the defect in either the steroidogenic acute regulatory (StAR) protein or the P450scc. More than 34 different mutations in StAR gene have been identified. Clinically, most of the patients manifest adrenal insufficiency from 1 day to 2 months of age, but some patient show delayed onset of adrenal insufficiency. Affected 46, XY subjects do not show pubertal development, whereas affected 46, XX subjects undergo spontaneous feminization, breast development and cyclical vaginal bleeding at the usual age of puberty. X-linked adrenal hypoplasia congenital (AHC) is a rare congenital adrenal disorder characterized by severe adrenal insufficiency and hypogonadotropic hypogonadism. More than 80 different several intragenic mutations of DAX-1 have been identified. The failure of pubertal development may be caused by either abnormal hypothalamic or pituitary regulation of gonadotropin secretion. In addition, although the testicular steroidogenesis is largely intact, the functional maturity of Sertoli cells and also spermatogenesis are impaired. The type of mutation does not predict clinical phenotype. Thus, unified mechanism how DAX-1 gene defect gives rise to adrenal insufficiency, hypothalamic/pituitary hypogonadism and impaired spermatogenesis remains established.

• Authors: Kenji Fujieda, Koji Okuhara, Shuji Abe, Toshihiro Tajima, Tokuo Mukai, Jun Nakae
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 85 Issue 2-5 Pg. 483-9 (Jun 2003) ISSN: 0960-0760 [Print] England
• PMID: 12943739 (Publication Type: Journal Article, Review)

Chemical References

• Phosphoproteins
• steroidogenic acute regulatory protein
• Cholesterol Side-Chain Cleavage Enzyme

Topics

• Adrenal Gland Diseases (genetics, physiopathology)
• Adrenal Hyperplasia, Congenital (genetics, physiopathology)
• Amino Acid Sequence
• Cholesterol Side-Chain Cleavage Enzyme (genetics)
• Humans
• Molecular Sequence Data
• Mutation
• Phosphoproteins (genetics)