Prevention of Ambiguous Genitalia in Congenital Adrenal Hyperplasia

Abstract

Ambiguous genitalia is not an uncommon problem in Saudi Arabia. [1][2][3] Its most common cause is congenital adrenal hyperplasia (CAH) caused by any one of the three inborn errors of steroidogenesis; 21-hydroxylase (the most common), 11β-hydroxylase, and 36-hydroxysteroid dehydrogenase deficiency in genetic female babies. 4 Advances in technology have made possible the prenatal diagnosis of CAH and subsequently, prenatal treatment with dexamethasone given to mothers throughout pregnancy and begun as early as possible has led to the prevention of virilization in at least three-fourths of affected infants. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] In this article, prenatal dexamethasone therapy was given to a Saudi mother of children with CAH due to 21-hydroxylase deficiency. This has prevented ambiguity in the second daughter. This is believed to be the first published local experience of this mode of prevention therapy. Case ReportA two-month-old male of a first-degree consanguineous couple presented with a history of recurrent vomiting and diarrhea and failure to thrive. He was found to have dehydration, hyponatremia, and hyperkalemia, and subsequently was diagnosed to have congenital adrenal hyperplasia due to 21-hydroxylase deficiency. He was therefore treated with hydrocortisone and 9-α -fluorocortisone. At the age of two years he was referred to the pediatric endocrine clinic at King Khalid University Hospital (KKUH), as per the wish of the family. Follow-up care was done and the parents were counseled.The mother then gave birth to her second infant, who has ambiguous genitalia ( Figure 1) and was immediately referred to KKUH for further management. She soon presented with hyponatremia and hyperkalemia. Appropriate replacement therapy was begun as explained above, with the addition of sodium chloride. Her chromosome analysis showed female karyotype (46,XX). Pelvic ultrasonography was not conclusive, but the genitogram showed female urethra. However, it had failed to visualize the uterus and the fallopian tubes. The 17-hydroxyprogesterone level was greater than 250 ng/mL (N = 0.21-1.4), androstendione level was 7.21 ng/mL (N=0.6-3.4), 11-deoxycorticosterone was 46.3 ng/mL (N=2.0-15), and renin >70 mg/mL/hr (N=0.68-1.38). Hormonal assay was performed in Bioscentia Laboratories (Germany). She then had clitoroplasty (clitoral recession) and vaginoplasty at one year of age, followed by vaginal dilatation at two and at three-and-one-half years of age.Despite some hesitation, after genetic counseling, the parents decided to have a third child. They were also informed at this stage about the preventive value of dexamethasone given to the mother during pregnancy and the very possible side effects which have been reported. At five weeks of gestation, the mother was placed on dexamethasone tablets 0.5 mg twice a day. At 16 weeks of gestation, she was subjected to amniocentesis, where the amniotic fluid chromosomal analysis showed 46,XY male karyotype. Dexamethasone was therefore disconti...