Familial male pseudohermaphroditism due to 5-alpha-reductase deficiency in a Turkish village.

Twelve persons with sexual ambiguity were identified in an isolated village in southern Turkey. Eleven were examined and had pseudovaginal perineoscrotal hypospadias; eight were studied. Serum and urine samples from five affected males and urine samples from three affected children were analyzed. Urine samples from another 26 villagers, mostly parents and siblings, were also analyzed. In all but one of the affected adult subjects, serum testosterone levels were either normal or increased, and in all adults, the dihydrotestosterone levels were low (8 to 20 ng/dl) and the testosterone/dihydrotestosterone ratios were elevated (to 36 or more); the levels of 4-androstenedione were normal. Thirty-four urine samples were analyzed for etiocholanolone/androsterone, 11-beta-hydroxyetiocholanolone/11-beta-hydroxyandrosterone, tetrahydrocorticosterone/5-alpha-tetrahydrocorticosterone and tetrahydrocortisol/5-alpha-tetrahydrocortisol ratios. In affected persons, all 5-beta/5-alpha urinary C19 and C21 steroid metabolite ratios measured were elevated. These findings are compatible with the diagnosis of male pseudohermaphroditism due to 5-alpha-reductase deficiency. In parents and some of the siblings of the affected subjects, the 5-beta/5-alpha urinary ratios were between affected and normal levels. The intermediate 5-beta/5-alpha ratios of the parents who were phenotypically normal, together with documented consanguinity, confirm an autosomal recessive mode of inheritance and are useful in identification of the carrier state. The urinary tetrahydrocortisol/5-alpha-tetrahydrocortisol ratios provided the highest index of discrimination between homozygotes (mean +/- SD, adults: 35.80 +/- 20.10; children: 15.48 +/- 7.91), heterozygotes (parents: 4.56 +/- 1.61; siblings and other relatives: 5.97 +/- 3.68), and normal subjects (1.07 +/- 0.36). Thus, this study identified a second community with inherited male pseudohermaphroditism due to 5-alpha-reductase deficiency, confirming the autosomal recessive inheritance of this condition and the generalized abnormality in both C19 and C21 steroid 5-alpha metabolism.