title: 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.affiliation: Department of Pediatrics, Asahikawa Medical College, 2-1-1-1 Midorigaoka, Higashi, Asahikawa 078-8510, Japan. ken-fuji@asahikawa-med.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
authors.forename: Koji
authors.initials: K
authors.lastname: Okuhara
authors.forename: Shuji
authors.initials: S
authors.lastname: Abe
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
authors.forename: Tokuo
authors.initials: T
authors.lastname: Mukai
authors.forename: Jun
authors.initials: J
authors.lastname: Nakae
mesh_terms: D000307:Adrenal Gland Diseases / Q000235:genetics* / Q000503:physiopathology; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics* / Q000503:physiopathology; D000595:Amino Acid Sequence; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D002786:Cholesterol Side-Chain Cleavage Enzyme