In the siblings reported, two affected boys have perineal hypospadias and bifid scrotum, and two affected girls have slight clitoral enlargement with otherwise normal genitalia. All are mild "salt losers" with spontaneous crises occurring late (3 months and 2 years) in the boys. The girls had negative sodium balance and hyponatremia only when stressed by salt deprivation at age 3 weeks and 4 years respectively. All had elevated 17-ketosteroid excretion when diagnosed, and in the two youngest, urinary dehydroisoandrosterone (DHA) exceeded androsterone. Cortisol production and/or 17-hydroxycorticosteroid excretions were normal. Steroid excretion patterns showed an increase of 3β-hydroxysteroid dehydrogenase (3-βHSD) activity with increased age, but with a persisting high excretion of pregrienetriol. At 2 months of age, one girl excreted per 24 hours: pregnanetriol–0.23 mg, pregnenetriol–1.2 mg, 17α- OH-pregnenolone–-2.6 mg, 16α-OH-pregnenolone– 8.2 mg, 16α-OH-DHA–5.4 mg, and DHA–0.5 mg. Her sister, at age 10 years, during withdrawal of cortisone therapy, excreted per 24 hours: pregnanetriol– 24 mg, pregnenetriol–14 mg, DHA–1.2 mg, and no 16αOH-pregnenolone or 16α-OH-DHA. We conclude that these patients have partial 3β-HSD deficiencies on the basis of inadequate fetal virilization and persistent postnatal excretion of large amounts of pregnenetriol. Possible explanations for the preponderance of urinary C-21 over C-19 steroids and for the large excretion of pregnanetriol are presented.
