Aromatase deficiency (AD) is a rare autosomal recessive disorder caused by CYP19A1 gene mutations and is characterized by lack of conversion of androgens to estrogens. Men usually present with continuing linear growth after puberty, tall stature, unfused epiphyses, delayed bone age, genu valgum, decreased bone mineral density, obesity, dyslipidemia, liver steatosis, insulin resistance, and impaired fertility. We here report a male case of aromatase deficiency with a novel CYP19A1 mutation.
A 30-year-old man with a tall stature (192 cm) presented with genu valgum. He complained to grow continuously. X-ray revealed incompletely fused epiphyses. Bone age was compatible with 14 years. Follicle-stimulating hormone and luteinizing hormone and testosterone were in normal ranges, but estradiol was undetectable. Insulin resistance as well as elevated serum alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase levels were found. Abdominal ultrasonography revealed steatohepatitis. In bone mineral density analysis, Z score was normal. The sperm count and vitality were normal. Sequencing of the CYP19A1 gene revealed a novel 6-base homozygote deletion in exon 10 (c.1465_1470del GAAATG). The parents and sister were heterozygous for the same mutation. Estrogen replacement therapy was started.
We report a male patient with AD who had a novel deletion in CYP19A1 gene. AD is an extremely rare condition. Till recently, all mutations have been in coding exons, mostly in exons 9 and 10. Estrogen replacement in AD has great impact on the recovery of dysplastic bone, lipid, liver, and glucose metabolism, but fails to improve insulin resistance. This will hopefully clarify the link between the deletion and the phenotype.