Snapshot A 13-year-old girl is evaluated by her pediatrician in the primary care clinic. She has severe acne that has been refractory to several treatment modalities. In addition, she reports having significant hair growth on her upper lip, chest, and armpits. Her voice has also become deeper in pitch in the past year. Her pediatrician has advised her to avoid playing contact sports, as her condition causes abnormal mineralization of her bones that may lead to fractures with minor trauma. She had genetic testing performed at birth, which revealed a mutation in the CYP19A1 gene. Introduction Overview aromatase deficiency is a disorder of sexual development characterized by decreased levels of estrogen and increased levels of testosterone Genetics inheritance pattern autosomal recessive mutations CYP19A1 gene Epidemiology Incidence < 1:1,000,000 fewer than 20 cases have been reported to date ETIOLOGY Pathophysiology mutation in the CYP19A1 gene, which codes for the enzyme aromatase aromatase converts androgens to estrogens ↓ aromatase activity leads to ↓ estrogen production and ↑ levels of androgens Presentation Symptoms both sexes hyperglycemia due to insulin resistance females lack of menstruation lack of breast growth Physical exam females infants ambiguous genitalia in female infants adolescence acne hirsutism during pregnancy maternal virilization excess fetal androgens may pass into the maternal bloodstream through the placenta males adolescence abnormal sperm production cryptorchidism abnormal bone growth Studies Gene sequencing will reveal a mutation in the CYP19A1 gene that codes for aromatase Differential 5α reductase deficiency key distinguishing factor 5α reductase deficiency is present only in genetic males (46,XY) testosterone and estrogen levels are normal Treatment Medical estrogen replacement females leads to menses, breast develompent, and proper bone growth males allows for proper bone growth Surgical surgical modification of ambiguous genitalia in females