Defects in steroid biosynthesis in adrenals and gonads lead to complex and profound clinical consequences that can be grouped in four categories: (1) defects of salt–water homeostasis and sexual development (DSD), (2) defects of salt–water homeostasis, (3) defects of sexual development, and (4) end-organ steroid hormone resistance. Among the members of the first group, lipoid adrenal hyperplasia is characterized by lack of all steroid hormones, with consequent 46, XY DSD and salt loss in the first weeks of life. 17a-Hydroxylase deficiency leads also to 46, XY DSD associated with hypertension and hypokalemia. 3b-Hydroxysteroid dehydrogenase deficiency causes incomplete virilization in male fetuses, together with salt loss. 21-Hydroxylase deficiency, whose nonclassic form is one of the most common autosomal recessive diseases in humans, is responsible for female ambiguous genitalia at birth and salt loss. 11b-Hydroxylase deficiency differs from 21-hydroxylase deficiency for the absence of salt wasting and later presence of hypertension and hypokalemia. Defects of P450 oxidoreductase, a cofactor common to 21-hydroxylase, 17a-hydroxylase, and aromatase, lead to a complex combined defect of all three enzymes.
Enzymatic defects of the second group cause either salt-wasting symptoms in the neonatal period, spontaneously resolving in adulthood, as in the case of corticosterone methyl oxidase II deficiency, or hypertension and hypokalemia as in the cases of glucocorticoid-suppressible hyperaldosteronism and apparent mineralocorticoid excess. The third group of defects includes enzymatic blocks of the last steps of sex hormones biosynthesis. 17,20-Lyase, 17b-hydroxysteroid dehydrogenase, 5a-reductase, and aldo-keto reductase deficiencies determine incomplete virilization of the male fetus. In 17,20-lyase deficiency, there is no spontaneous puberty in males and females; in the latter two male puberty occurs. Aromatase deficiency is a cause of nonadrenal 46, XX DSD. The end-organ resistance syndromes, which are still an exclusion diagnosis, represent a further challenge for future diagnostic and therapeutic applications. The treatment of these defects is based on exogenous administration of the deficient hormones and corrective surgery in intersexuality. Given the rarity of most of these diseases, prenatal diagnosis is possible only in a family at risk. In the case of 21-hydroxylase deficiency, however, advances in prenatal diagnosis allowed in utero treatment. Progress in molecular analysis of steroid biosynthesis and action defects will allow a better prenatal diagnosis and treatment of such diseases.
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Antley R, Bixler D (1975) Trapezoidocephaly, midfacial hypoplasia and cartilage abnormalities with multiple synostoses and skeletal fractures. Birth Defects Orig Artic Ser 11:397–401PubMedGoogle Scholar
Biason-Lauber A, Suter SL, Shackleton CH, Zachmann M (2000) Apparent cortisone reductase deficiency: a rare cause of hyperandrogenemia and hypercortisolism. Horm Res 53:260–266, 23577PubMedCrossRefGoogle Scholar
Conte FA, Grumbach MM, Ito Y, Fisher CR, Simpson ER (1994) A syndrome of female pseudohermaphroditism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom). J Clin Endocrinol Metab 78:1287–1292PubMedGoogle Scholar
Crisponi G, Porcu C, Piu ME (1997) Antley-Bixler syndrome: case report and review of the literature. Clin Dysmorphol 6:61–68PubMedCrossRefGoogle Scholar
Geller DS, Rodriguez-Soriano J, Vallo Boado A, Schifter S, Bayer M, Chang SS, Lifton RP (1998) Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. Nat Genet 19:279–281. doi:10.1038/966PubMedCrossRefGoogle Scholar
Imperato-McGinley J, Gautier T, Peterson RE, Shackleton C (1986) The prevalence of 5 alpha-reductase deficiency in children with ambiguous genitalia in the Dominican Republic. J Urol 136:867–873PubMedGoogle Scholar
Lin D, Sugawara T, Strauss JF 3rd, Clark BJ, Stocco DM, Saenger P, Rogol A, Miller WL (1995) Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science 267:1828–1831PubMedCrossRefGoogle Scholar
Lipsett MB, Tomita M, Brandon DD, De Vroede MM (1986) Cortisol resistance in men. In: Chrousos GP, Loriaux MB (eds) Steroid hormone resistance: mechanism and clinical aspects. Plenum Press, New YorkGoogle Scholar
McPhaul MJ, Griffin JE (1999) Male pseudohermaphroditism caused by mutations of the human androgen receptor. J Clin Endocrinol Metab 84:3435–3441PubMedGoogle Scholar
New MI (1994) The prismatic case of apparent mineralocorticoid excess. J Clin Endocrinol Metab 79:1–3PubMedGoogle Scholar
New MI, White PC, Pang SA, Dupont B, Speiser PW (1989) The adrenal hyperplasias. In: Beaudet AR, Scriver CR, Sly W, Valle D (eds) The metabolic basis of inherited disease. McGraw-Hill, New YorkGoogle Scholar
Peterson RE, Imperato-McGinley J, Gautier T, Shackleton C (1985) Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases. A new variant of congenital adrenal hyperplasia. N Engl J Med 313:1182–1191PubMedCrossRefGoogle Scholar
Prader A, Gurtner HP (1955) The syndrome of male pseudohermaphroditism in congenital adrenocortical hyperplasia without overproduction of androgens (adrenal male pseudohermaphroditism). Helv Paediatr Acta 10:397–412PubMedGoogle Scholar