Aromatase deficiency

Aromatase deficiency is a rare condition characterized by extremely low levels or complete absence of the enzyme aromatase activity in the body. It is an autosomal recessive disease resulting from various mutations of gene CPY19 (P450arom) which can lead to ambiguous genitalia and delayed puberty in females, continued linear growth into adulthood and osteoporosis in males and virilization in pregnant mothers. As of 2020, fewer than 15 cases have been identified in genetically male individuals and at least 30 cases in genetically female individuals. The deficiency causes the virilization of XX fetuses. The onset of symptoms usually occurs in adolescence or early adulthood. The lack of estrogen results in the presentation of primary amenorrhea and tall stature. The taller than expected height occurs because estrogen normally causes fusion of the epiphyseal growth plates in the bones, and in its absence, the patient will keep growing longer. The gonadotropins LH and FSH will both be elevated and patients present with polycystic ovaries. Furthermore, the low oestrogen will predispose those with the condition to osteoporosis. After birth, female infants usually display ambiguous genitalia including labioscrotal fusion, clitoromegaly, and phallic genitalia. Hyperandrogenism is present at birth along with low level of estrogen in the blood. However, they have normal internal female genitalia. Known cases presented with Prader scale ratings between II and V, with most classified as IV (11 out of 23 cases) or III (7 out of 23 cases). Some 46,XX individuals are assigned male at birth because of sufficiently virilized genitalia and a male gender identity persisted in a subset of these cases. During pubertal age, progressive sign of virilization such as growing of body hair can be observed along with puberty failure due to the lack of estradiol action. The disruption of the LHRH-LH/FSH axis causes bone age to delay with the absence of growth spurt. In adulthood, symptoms include virilization, absence of breast development, primary amenorrhea and infertility, and multicystic ovaries.