Endocrine and biochemical studies in a 46,XY phenotypically male infant with 17-ketosteroid reductase deficiency

A 46,XY phenotypically male patient with 17-ketosteroid reductase deficiency is described. The patient was a 6-month-old infant who presented with micropenis and bilateral cryptorchidism. Baseline plasma levels of testosterone (T), delta 4-androstenedione (delta 4A), and 5 alpha-dihydrotestosterone (5 alpha-DHT) were within the normal range [patient: 0.17 (T), 0.12 (delta 4A), and 0.032 (5 alpha-DHT) ng/ml; normal infants: 0.03-0.55 (T), 0.14-0.45 (delta 4A), and 0.01-0.23 (5 alpha-DHT) ng/ml]. hCG administration induced a significant rise in plasma delta 4A levels (up to 8.39 ng/ml) and a slight increase in T and 5 alpha-DHT levels. The delta 4A/T ratios before and during the hCG challenge were 0.86 and 55.61, respectively (controls: 0.83 and 0.13). Incubation of genital skin-derived fibroblasts from the patient with either [3H]T or [3H] delta 4A revealed normal formation of delta 4A from T and diminished conversion of delta 4A to T. The development of a male phenotype despite both a testicular and peripheral 17-ketosteroid reductase deficiency is difficult to explain. It is possible that the fetal testes were the source of sufficient amounts of T during the early periods of embryonic life, and that late onset of the enzyme deficiency prevented the development of completely normal male genitalia. The in vitro finding of normal T to delta 4A conversion by the mutant fibroblasts suggests that in this particular tissue 17 beta-reduction and dehydrogenation of androgens are mediated by two isoenzymes with distinct substrate and/or cofactor specificities.