Background: Aromatase deficiency is a rare autosomal recessive disorder produced by CYP19 gene mutations. 46XX affected patients presented with ambiguous genitalia leading to early identification. Most 46XY affected patients presented normal external genitalia and the condition often remains undiagnosed until late puberty. Information on pubertal development in affected boys is scarce since to the present date only two patients, younger than 4 years of age, without long-term follow-up, had being reported.
Objective and hypotheses: We report the clinical phenotype and hormonal studies of a 46,XY aromatase deficient boy.
Results: Molecular analysis revealed a previously reported homozygous mutation (R192C) in the CYP19 gene, predicted to compromise enzyme function. The patient was the oldest brother of a 46XX affected sister. Maternal virilisation was present during both pregnancies. First evaluation at 7.9 years: 3 years delayed bone age was the only remarkable finding observed. Laboratory tests showed normal prepubertal basal serum gonadotropin (including an adequate GnRH stimulation test), inhibin B, AMH, testosterone and androstendione levels. OGTT was normal as well as bone mass, assessed by DEXA. The patient was lost in follow-up and returned at 11.3 years of age with signs of advanced puberty (Tanner stage IV, testicular volume 12/15 ml). Bone age was 2 years delayed. Laboratory tests revealed normal pubertal basal and GnRH stimulated gonadotropin levels and increased serum testosterone (5.9 ng/ml, male reference range for Tanner IV: 15.4 ng/ml).
Conclusion: Normal pubertal development was referred in adult men with aromatase deficiency. Interestingly our patient presented with precocious/early and accelerated puberty and apparently normal pituitary gonadal function. Estrogen restrain on gonadotropin secretion has been demonstrated in animal and human models of estrogen deficiency operating since early phases of puberty in males. This human model of nature suggests that aromatase activity at hypothalamic level is required to define pubertal tempo and/or the time of puberty onset in boys.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology