Genetic and Clinical Spectrum of Aromatase Deficiency in Infancy, Childhood and Adolescence

BELGOROSKY, A; GUERCIO G.,; PEPE C,; SARACO N,; RIVAROLA MA,

HORMONE RESEARCH

KARGER

Año: 2009 vol. 72 p. 312 - 330

0301-0163

ABSTRACT Information derived from reviewing the phenotype of aromatase deficiency provides clues for understanding the role of aromatase in prepubertal and pubertal human health and disease. Placental aromatization of androgens protects the female fetus against the virilizing action of fetal androgens. The dual effect of aromatase-deficiency, excessive androgens and insufficient estrogens, makes it difficult to dissect the cause of the derangement. In newborns lack of aromatase is one etiology of 46,XX DSD. In girls, aromatase plays an important role in regulating the hypothalamic-pituitary-gonadal axis. Aromatase-deficient girls are exposed to high levels of ovarian androgens under abnormal gonadotropin stimulation, facilitating the formation of ovarian cysts. Use of low-dose estrogens has variable results. Inhibition of LH and FSH with GnRH analogs might be necessary. Bone mineralization can be affected and bone age is delayed. At puberty in girls, there is no or scarce sexual development, as well as abnormal virilization. The phenotype can be variable, as a consequence of the 24 different reported mutations, affecting enzyme activity to different degrees. Insulin sensitivity can be abnormal in both men and women. Finally, aromatase could also play a programming role in the fetal and newborn testis.