Congenital adrenal hyperplasia due to 17-alpha-hydoxylase/17, 20-lyase deficiency presenting with hypertension and pseudohermaphroditism: first case report from Oman

ABSTRACT

This is the first report of congenital adrenal hyperplasia [CAH] due to combined 17 alpha-hydroxylase/17, 20 lyase deficiency in an Omani patient who was initially treated for many years as a case of hypertension. CAH is an uncommon disorder that results from a defect in steroid hormones biosynthesis in the adrenal cortex. The clinical presentation depends on the site of enzymatic mutations and the types of accumulated steroid precursors. A 22-year-old woman who was diagnosed to have hypertension since the age of 10 years who was treated with anti-hypertensive therapy was referred to the National Diabetes and Endocrine Centre, Royal Hospital, Oman. The patient also had primary amenorrhea and features of sexual infantilism. Full laboratory and radio-imaging investigations were done. Adrenal steroids, pituitary function and karyotyping study were performed and the diagnosis was confirmed by molecular mutation study. Laboratory investigations revealed adrenal steroids and pituitary hormones profile in addition to 46XY karyotype that are consistent with the diagnosis of CAH due to 17 alpha-hydroxylase deficiency. Extensive laboratory workup revealed low levels of serum cortisol [and its precursors 17 alpha-hydroxyprogesterone and ll'deoxycortisol], adrenal androgens [dehydroepiandrosterone sulfate and androstenedione], and estrogen [estradiol]; and high levels of mineralocorticoids precursors [11-deoxycorticosterone and corticosterone] with high levels of ACTH, FSH and LH. Mutation analysis revealed CYP17Al-homozygous mutation [c.287G>A p.Arg96Gln] resulting in the complete absence of 17 alpha-hydroxylase/17, 20-lyase activity. The patient was treated with dexamethasone and ethinyl estradiol with cessation of anti-hypertensive therapy. A review of the literature was conducted to identify previous studies related to this subtype of CAH. This is the first biochemically and genetically proven case of CAH due to 17 alpha-hydroxylase/17, 20-lyase deficiency in Oman and in the Arab World described in the literature