Inheritance: autosomal recessive
Affected gene: CYP19A1
Affected enzyme: aromatase cytochrome P450 (P450arom)
Consequence of mutation: defect in the final step in the conversion of C19 steroids to estrogens, resulting in low estrogen and high androgen levels
Clinical features:
(1) virilization at birth (female pseudohermaphroditism)
(2) delayed epiphyseal closure/fusion with delayed bone age
(3) tall stature, starting with puberty
(4) osteopenia and osteoporosis with recurrent bone fractures
(5) pubertal failure
(6) virilization (acne, cliteromegaly, hirsutism, deepening of the voice, male pattern hair loss)
(7) hypergonadotrophic hypogonadism with cystic ovaries
(8) variable acanthosis nigricans
Laboratory findings:
(1) no excess in growth hormone
(2) high normal or elevated serum testosterone
(3) high normal or elevated gonadotropins (FSH, LH)
(4) low serum estrogens
(5) variable hyperinsulinemia
Differential diagnosis:
(1) polycystic ovary syndrome (PCOS)
