Partial 3β-hydroxysteroid Dehydrogenase (3β-HSD) and 21-hydroxylase Deficiencies in a Family With Congenital Adrenal Hyperplasia, With Evidence for Increasing 3β-HSD Activities with Age

Abstract

In this family, 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 Na+ balance only when stressed by salt deprivation at ages 2 months and 4 years. All had elevated 17-ketosteroid excretion when diagnosed and, in the 2 youngest, urinary DHA > androsterone. Cortisol production and/or 17-OH-corticosteroid excretions were normal. Steroid excretion patterns showed an increase of 3β-HSD activity with increased age, but with a persisting high excretion of Δ⁴-pregnanetriol (Δ⁵-p′triol). At 2 months, one girl excreted per 24 h: pregnanetriol (p′triol)-0.23 mg, Δ⁵-p′triol-1.2 mg, 17α-OH-pregnenolone-2.6 mg, 16α-OH-pregnenolone-8.2 mg, 16α-OH-DHA-5.4 mg, DHA-0.5 mg. Her sister, at age 10 years, during withdrawl of cortisone therapy, excreted per 24 h: p′triol-24 mg, Δ⁵-p′triol-14 mg, DHA-1.2 mg, no 16α-OH-pregnenolone or 16α-OH-DHA. We conclude that these cases have partial 3β-HSD deficiencies, on the basis of the inadequate fetal virilization and persistent post-natal excretion of large amounts of Δ⁵-′triol; and partial 21-hydroxylase deficiencies, on the basis of the high p′triol excretions. The low post-natal excretion of DHA, relative to Δ⁵-p′triol and 17α-OH-pregnenolone, may be due to a late fetal appearance of the 3β-HSD for DHA or may be due to an underactivity of the 17–20 desmolase (side-chain splitting) enzyme.

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