Mixed Gonadal Dysgenesis Most patients with mixed gonadal dysgenesis are XY and have ambiguous genitalia with a streak gonad on one side and a malformed testis on the opposite. A small proportion of these patients have mutations in the SRY gene (17).
Congenital Lipoid Adrenal Hyperplasia Patients with this autosomal recessive disorder are unable to convert cholesterol to pregnenolone, which is the first step in steroid hormone biosynthesis. A defect was not found in the P450scc gene, which is the conversion enzyme responsible for this step in the pathway. Instead, 15 different mutations were identified in the steroidogenic acute regulatory protein (StAR), which facilitates the transport of cholesterol from the outer to the inner mitochondrial membrane. This protein appears to be the rate-limiting step for steroid hormone biosynthesis stimulated by tropic hormones. These patients present in infancy with hyponatremia, hyperkalemia, and acidosis. Both XX and XY individuals are phenotypically female. Genetic clusters of the disorder are found in the Japanese, Korean, and Palestinian Arab populations. With appropriate mineralocorticoid and glucocorticoid replacement, these patients can survive into adulthood. Most patients are XY and do not have a uterus. Without hormone replacement, they remain sexually infantile. XX patients may acquire secondary sexual characteristics at puberty but develop large ovarian cysts and early ovarian failure (24,25).
17´a-Hydroxylase and 17,20-lyase Deficiency Mutations in the CYP17 gene cause abnormalities in both the 17α-hydroxylase and 17,20-lyase functions of the protein that is active in the adrenal and gonadal steroidogenic pathways. More than 20 mutations that alter the reading frame of the gene are identified, even though very few people have the disorder (26). Patients have either 46,XX or 46,XY karyotypes. The uterus is absent in individuals with 46,XY karyotype, a feature distinguishing them from individuals with the 46,XX karyotype. Individuals with CYP17 mutations have primary amenorrhea, no secondary sexual characteristics, female phenotype, hypertension, and hypokalemia (27). The diminished levels of 17α-hydroxylase that characterize this disorder lead to a reduction in cortisol production, which in turn causes an increase in adrenocorticotropic hormone (ACTH). 17-hydroxylase is not required for production of mineralocorticoids; thus, excessive amounts of mineralocorticoid are produced, resulting in sodium retention, loss of potassium, and hypertension. Patients with 17α-hydroxylase deficiency have primordial follicles, but gonadotropin levels are elevated because the enzyme deficiency prevents synthesis of sex steroids.