Rare Types of Congenital Adrenal Hyperplasias Other Than 21-hydroxylase Deficiency

Abstract

Although the most common cause of congenital adrenal hyperplasia (CAH) worldwide is 21-hydroxylase deficiency (21-OHD), which accounts for more than 95% of cases, other rare causes of CAH such as 11-beta-hydroxylase deficiency (11β-OHD), 3-beta-hydroxy steroid dehydrogenase (3β-HSD) deficiency, 17-hydroxylase deficiency and lipoid CAH (LCAH) may also be encountered in clinical practice. 11β-OHD is the most common type of CAH after 21-OHD, and CYP11B1 deficiency in adrenal steroidogenesis causes the inability to produce cortisol and aldosterone and the excessive production of adrenal androgens. Although the clinical and laboratory features are similar to 21-OHD, findings of mineralocorticoid deficiency are not observed. 3β-HSD deficiency, with an incidence of less than 1/1,000,000 live births, is characterized by impairment of both adrenal and gonadal steroid biosynthesis very early in life, with inadequate virilization in boys and varying degrees of virilization in girls. It may present with salt wasting crisis or delayed puberty in both genders. While 46,XY disorders of sex development is frequently observed in boys with 17-hydroxylase deficiency, immature pubertal development and primary amenorrhea are observed in girls due to estrogen deficiency throughout adolescence. Patients with LCAH, which develops due to steroidogenic acute regulatory protein deficiency, typically present with salt wasting in the first year of life. It is characterized by complete or near-complete deficiency of adrenal and gonadal steroid hormones and progressive accumulation of cholesterol esters in the adrenal gland.