Adrenogenital syndrome in Infant/Neonate
21-Hydroxylase deficiency accounts for 95% of all cases of CAH and is inherited in an autosomal recessive pattern. It is due to a mutation of the CYP21 gene. It can occur in a classical or nonclassical form. The incidence of the classical form of CAH is roughly 1:15 000, while that of the nonclassical form is approximately 1:100. Classical CAH can be further divided into a salt-wasting form (75%) and a simple virilizing form (25%). 21-Hydroxylase is necessary for the production of cortisol and aldosterone. Lack of this enzyme shunts intermediate steroid precursors toward androgen production. Symptoms are related to excess androgens and, in the salt-wasting form of classical CAH, decreased aldosterone. Aldosterone is necessary for normal sodium retention and potassium secretion by the kidney.
For more information, see OMIM.
E25.0 – Congenital adrenogenital disorders associated with enzyme deficiency
267395000 – Adrenogenital syndrome
17-Alpha-hydroxylase deficiency is a rare cause of congenital adrenal hyperplasia that leads to a decrease in adrenal androgen synthesis and an increase in aldosterone, causing renal reabsorption of sodium, hypertension, and hypokalemia. Males present with ambiguous external genitalia at birth. Females present with delayed puberty, amenorrhea, and failure to develop breasts and pubic hair. These patients will have low urine 17-ketosteroid and high urine gonadotropin levels. Treatment is with dexamethasone to suppress pituitary ACTH secretion and testosterone to aid with sexual maturation.
3-Beta-hydroxysteroid dehydrogenase deficiency is another rare cause of congenital adrenal hyperplasia that results in decreased production of all three groups of adrenal hormones, including mineralocorticoids, glucocorticoids, and sex steroids. This leads to salt wasting in both males and females, and ambiguous genitalia in males.
Polycystic ovarian syndrome can present with hirsutism, acne, and menstrual irregularities, but these patients will not have increased serum 17-hydroxyprogesterone, classical electrolyte abnormalities (hyponatremia, hyperkalemia), or increased urine 17-ketosteroids.
5-Alpha-reductase deficiency can cause ambiguous genitalia in male neonates because of a lack of conversion of testosterone to the more physiologically active dihydrotestosterone. At puberty, these patients may partially virilize.
Androgen insensitivity syndrome can cause ambiguous genitalia in male neonates, but prenatal undervirilization occurs with absence of pubic and axillary hair and lack of acne.