We identified a new point mutation in the
CYP19 gene responsible for
aromatase (
P450arom) deficiency in a 46,XY male infant with unremarkable clinical findings at birth. This boy is homozygote for a 1-bp (C) deletion in exon 5 of the
aromatase gene causing a frame-shift mutation. The frame-shift results in a prematurely terminated
protein that is inactive due to the absence of the functional regions of the
enzyme.
Aromatase deficiency was suspected prenatally because of the severe
virilization of the mother during the early pregnancy, and the diagnosis was confirmed shortly after birth. Four weeks after birth, the baby boy showed extremely low levels of serum
estrogens, but had a normal level of serum free
testosterone; in comparison with the high serum concentration of
androstenedione at birth, a striking decrease occurred by 4 weeks postnatally. We previously reported elevated basal and stimulated FSH levels in a female infant with
aromatase deficiency in the first year of life. In contrast, in the male infant, basal FSH and peak FSH levels after standard
GnRH stimulation tests were normal. This finding suggests that the contribution of
estrogen to the hypothalamic-pituitary
gonadotropin-gonadal feedback mechanism is different in boys and girls during infancy and early childhood. In normal girls, serum
estradiol concentrations strongly correlate with circulating
inhibin levels, and thus, low
inhibin levels may contribute to the striking elevation of FSH in young girls with
aromatase deficiency. In contrast,
estradiol levels are physiologically about a 7-fold lower in boys than in girls, and serum
inhibin levels remain elevated even though levels of FSH, LH, and
testosterone are decreased.