Journal article Open Access
Human aromatase deficiency is a very rare disease caused by CYP19A1 aromatase gene mutations resulting in congenital estrogen deprivation. The substantial clinical experience of the presentation, diagnosis and intervention is reviewed in order to describe in a systematic way the clinical aspects of the disease in men and to provide useful clinical advice for its management. At presentation, the clinical features common to all aromatase-deficient men are: tall stature, delayed bone maturation, osteopenia/osteoporosis, and eunuchoid skeleton. The diagnosis is almost always delayed and generally is made during adulthood. An adequate clinical path allows to confirm or reject the clinical diagnosis in all patients suspected with the disease. Unfused epiphyses and undetectable serum estradiol support a clinical diagnosis, the genetic sequencing of the CYP19A1 gene further substantiating the diagnosis. Transdermal estradiol treatment and a dosage of 0.22-0.35 μg/kg should be considered as adequate for replacement therapy and continued lifelong. Serum estradiol, luteinizing-hormone (LH), testosterone and bone mineral density (BMD) should be carefully monitored and considered, in clinical practice, as powerful biochemical markers of adequate estrogen substitution and. The gold standard for starting estrogen treatment seems to be puberty and early diagnosis should be advocated to avoid disease overlook and undermanagement.