Although
POR deficiency (PORD) is assumed to be accompanied by excessive placental
androgen accumulation and enhanced adrenal and testicular
androgen production via the backdoor pathway as well as compromised testicular
androgen production via the frontdoor pathway, there is no direct evidence for the flux of excessive placental
androgens into the fetal circulation and for the production of
dihydrotestosterone (DHT) via the backdoor pathway. We examined longitudinal serum and urine
steroid metabolite profiles in a 46,XY infant with PORD who was prenatally identified because of the progressive fetal masculinization and maternal
virilization from the mid-gestation and the presence of fetal radio-humeral
synostosis and was confirmed to have compound heterozygous mutations of POR (p.Q201X and p.R457H). The results showed (1) markedly and inappropriately elevated serum
androstenedione and
testosterone (T) values at birth, (2) a markedly increased serum DHT value with a normal DHT/T ratio at birth, (3) transient elevation of serum T and DHT values accompanied by a normal DHT/T ratio and concomitant elevations of intermediate
steroid metabolites on both the frontdoor and backdoor pathways at 30 days of age, and (4) persistent PORD-compatible urine
steroid profiles. Although the data obtained from a single infantile patient are too premature to be generalized, they imply: (1) the transfer of excessive placental
androgens into the fetal as well as the maternal circulations from the mid-gestation, (2) lack of a clinically discernible amount of DHT production via the adrenal backdoor pathway around birth, and (3) the activation of both the frontdoor and backdoor pathways in the testis around the mini-puberty, with no production of a clinically discernible amount of DHT via the testicular backdoor pathway.