Congenital Adrenal Hyperplasia (CAH) refers to a complex series of rare but well-studied enzymatic errors of metabolism with deficient levels of different enzymes involved in the synthesis of cortisol (hydrocortisone).
CAH comprises a group of disorders resulting from defective synthesis of adrenal corticosteroids. Lack of glucocorticoids, especially cortisol, causes various kinds of metabolic problems. The response to low levels of cortisol is increased production of corticotropin (ACTH). Lack of mineralocorticoids, primarily aldosterone (steroid hormone), causes sodium and water imbalance which, in some cases, can be fatal. The various forms of CAH represent defects in the different stages of corticosteroid synthesis, usually hydroxylation reactions at certain positions on the original CAH is a family of inherited disorders affecting the adrenal glands. The most common form is 21-hydroxylase deficiency (21-OHD), which is inherited in severe or mild forms. The severe form, called Classical CAH, is usually detected in the newborn period or in early childhood. The milder form, called Non-classical CAH (NCAH), may cause symptoms at anytime from infancy through adulthood. NCAH is a much more common disorder than Classical CAH. Fortunately, CAH can be managed with medication and, with adequate care, affected individuals go on to live normal lives.
CAH is an autosomal recessive genetic disorder. It affects males and females in equal numbers. For a child to be born with either form of CAH, both parents must carry a gene for the disorder (see Figure 1). Scientists have pinpointed the location of the group of genes that causes the most common forms of CAH to chromosome 6. DNA testing is available for diagnosis of CAH and to detect carriers of the gene mutations.
These particular groups of genes contain instructions the adrenal glands (located on top of the kidneys) need in order to produce an enzyme called 21-hydroxylase. Without this enzyme, the adrenal glands are unable to produce cortisol, a hormone necessary for life. In addition, over 75 percent of all individuals with Classical_CAH also lack another adrenal hormone called aldosterone, necessary for maintaining normal fluid volume of the body, sodium and potassium, which among other functions, stabilizes the heart. When this deficiency occurs it is called “Salt-Wasting CAH” (SW-CAH). The remaining 25 percent of those with Classical CAH who produce sufficient aldosterone are referred to as “Simple Virilizers” (SV-CAH). The Nonclassical form ofCAH is not life threatening but can affect: (1) puberty and growth in children, and (2) cause infertility in males and females as well as other symptoms affecting quality of life. Other rare forms of enzyme deficiency that belong to the Congenital Adrenal Hyperplasia family of disorders are: 3Beta-hydroxysteroid dehydrogenase deficiency (3B-HSD), 11-Beta hydroxylase deficiency (11B-HD) and 17-alpha hydroxylase deficiency (17a-HD) which are much less common. This website focuses on 21-OH deficiency, as it is the most common form of the disorder. Before 20th century, an Italian anatomist, Luigi De Crecchio provided the earliest known description of a case of probable CAH. “I propose in this narrative that it is sometimes extremely difficult and even impossible to determine sex during life. In one of the anatomical theaters of the hospital..., there arrived toward the end of January a cadaver which in life was the body of a certain Joseph Marzo... The general physiognomy was decidedly male in all respects. There were no feminine curves to the body. There was a heavy beard. There was some delicacy of structure with muscles that were not very well developed... The distribution of pubic hair was typical of the male. Perhaps the lower extremities were somewhat delicate, resembling the female, and were covered with hair... The penis was curved posteriorly and measured 6 cm, or with stretching, 10 cm....