Prepubertal diagnosis of steroid 5 alpha-reductase deficiency.
The diagnosis of 5 alpha-reductase deficiency was proven in two prepubertal patients with male pseudohermaphroditism (MPH). Both had a 46-XY karyotype and were reared as females; one child had been castrated in infancy. Clitoromegaly, urogenital sinus, and short vaginal pouch were present in both; inguinal gonads were palpable in one. The diagnosis was made biochemically by observing characteristic changes in five parameters: 1) abnormally high testosterone to dihydrotestosterone (T:DHT) ratio after hCG stimulation (35 and 53 vs. normal, 11 +/- 3), 2) abnormally high 5 beta-T metabolites in urine (8.1 and 6.0 vs. normal, less than 1),3) deficient conversion of T to DHT during [3H] T infusion (0.3 and 0.4% vs. normal, 5.3 +/- 3), 4) deficient conversion of [14 C] T to 5 alpha-reduced metabolites by nongenital skin fibroblasts (2.2 and 1.9 pmol/microgram DNA/nmol substrate vs. 68.4+/- 7.8 Pmol/microgram DNA/nmol substrate in normal controls), and 5) deficient conversion of [14C]T to DHT in genital skin slices. The fact that this syndrome represents a defect in T metabolism rather in in T binding is demonstrated by the observation that binding of [3H]DHT to cytosol of skin fibroblasts was normal (4.2 dpm/micrograms DNA vs. normal male values of 3.7 +/- 0.64). Thus, the present report suggests that 5 alpha-reductase deficiency can be diagnosed during childhood and even after castration by metabolic studies of nongenital skin fibroblasts and determination of the conversion ratio of [3H]T to [3H]DHT in plasma.
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency*; D000728:Androgens / Q000652:urine; D002369:Castration; D002478:Cells, Cultured; D002648:Child; D006063:Chorionic Gonadotropin; D004247:DNA / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D012734:Disorders of Sex Development / Q000201:enzymology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007621:Karyotyping; D008297:Male; D010088:Oxidoreductases / Q000172:deficiency*; D011627:Puberty; D012867:Skin / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D006063:Chorionic Gonadotropin; D013196:Dihydrotestosterone; D013739:Testosterone; D004247:DNA; D010088:Oxidoreductases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase