Background: The most common form of congenital adrenal hyperplasia (CAH) is 21-hydroxylase deficiency, which in its severe form can cause genital ambiguity in females. This can be ameliorated by administering dexamethasone to the mother.
Case: This is a family whose index case is a first son diagnosed by Madrid Newborn Screening Program of CAH with salt-wasting form due to 21-hydroxylase deficiency. Mutation analysis revealed: hybrid deletion includes the 655G splicing mutation at intron 2 and 8 pairs deletion of exon 3 from paternal line and a large conversion of the gene in maternal line. Both mutations are a severe type and involve significant virilization. In her second pregnancy, dexamethasone treatment is initiated at 4+5 weeks gestation. The dose administered was 23 μg/kg per day. At 9 week gestation chorionic villous sampling confirmed female foetus affected (46XX) by CAH (same mutations as her brother) so mother was treated until term. Pregnancy was unremarkable until 31 weeks gestation when spontaneous rupture of membranes. Birth weight was 950 g (−2.06DS) and height 35.5 cm (−2.47DS). Genitalia was assessed as normal at birth, with hypertrophied clitoris according to her prematurity. At 16 days of age her 17OHP concentration was elevated (163 μg/l) and symptoms of salt-losing form were detected. She was administered hydrocortisone (150 mg/m2 per day), fludrocortisone (0.025 mg/day) and ClNa (45 mEq/kg per day). Maternal side effects of dexamethasone administration were weight gain and facial acne. Gestational diabetes was not attributed clearly to the treatment performed. Foetal exposure to dexamethasone may be related to intrauterine growth restriction and preterm labour.
Conclusion: Prenatal treatment seems to prevent the gender ambiguity sometimes seen in CAH females. Treatment is offered to women who have previously given birth to a child with severe CAH. Treatment should only be undertaken when the follow-up in the newborn is documented by competent pediatricians experienced with CAH.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology