Genetics of Congenital Adrenal Hyperplasia (CAH)

Abstract
Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders of the adrenal hormone synthesis. Hereditary deficiency of the enzymes, involved in biosynthesis of the adrenal hormones, such as cortisol, aldosterone and androgens, leads to structural and functional malformations. These malformations begin in utero and are prominent at birth. Deficiency or complete absence of the steroid hormone depends on the type of genetic mutation. In the vast majority of the cases, only cortisol synthesis is affected. In such cases, deficiency of cortisol stimulates release of the ACTH (adreno-corticotropic hormone) from the anterior pituitary gland, which in turn, stimulates growth and enlargement of the adrenal tissue - adrenal hyperplasia. Adrenal hyperplasia then results in increased production of other adrenal hormones - aldosterone and/or androgens. Increased aldosterone causes increased sodium retention, which leads to increased blood pressure, whereas increased androgens stimulate abnormal virilization of females and excessive masculinization of males. In the past, classic CAH was fatal early in infancy, but with modern treatment options, affected individuals have normal live-span. Mild to moderate symptoms and related conditions are present in most of the affected individuals through their entire life. Such symptoms may include short stature in both, males and females, hyperandrogenic syndrome in females, and symptoms of excess androgens in males. Both genders may have early-onset hypertension and sodium/potassium imbalances. Course of the disease depends on the type of CAH. While in classic CAH, cortisol is deficient and other adrenal hormones are elevated, in other types of CAH, which originate from different genetic mutations, cortisol levels may be normal, but aldosterone or testosterone may be deficient. Presenting clinical symptoms and onset of the disease in such cases correlate with the deficiency or excess of the specific hormones.

Read full article for:

• Introduction to CAH (Part I)
• Symptoms of CAH (Part I)
• Types of CAH (Part I)
• CAH due to 21 hydroxylase deficiency: genetics, incidence rates and symptoms
• CAH due to 11-beta hydroxylase deficiency: genetics, incidence rates and symptoms
• CAH due to 17-alpha hydroxylase deficiency: genetics of global adrenal deficiency
• 3-beta hydroxysteroid dehydrogenase deficiency: rare and severe type of CAH
• Lipoid adrenal hyperplasia: specific genetic mutations and symptoms
• Aldosterone synthase deficiency
• Mortality and Morbidity Rates for CAH (Part II)
• Diagnostic Testing (Part II)
• Treatment Options (Part II)
• Gene Therapy as Potential Treatment (Part II)