Adrenal Hyperplasia, Congenital, Due to 21-Hydroxylase Deficiency
Victor A. McKusick, OMIM, Johns Hopkins University, May 21, 2008
[for Professionals mainly]
Congenital Adrenal Hyperplasia;
Cytochrome P450, Subfamily XXIA;
Cytochrome P450, Subfamily XXI;
Steroid Cytochrome P450 21-Hydroxylase;
21 Hydroxylase B, Included ...
Gene Map Locus: 6p21.3 ... Since the symbol CAH is used for all forms of congenital adrenal hypoplasia (240200, 300200) and since CAH1 contains no intrinsic information indicating the particular type of adrenal hyperplasia, CA21H enjoyed favor as the preferred symbol after about 1983. Regarding nomenclature of the gene, the functional gene, previously designated CYP21B, is symbolized simply as CYP21, and the nonfunctional gene, previously CYP21A, is symbolized CYP21P (for pseudogene) (McAlpine, 1988) ... There are 4 recognized clinical forms of congenital adrenal hyperplasia, the majority of cases being associated with 21-hydroxylase deficiency: salt-wasting (SW), simple virilizing (SV), nonclassic (NC) late-onset (also called attenuated and acquired), and cryptic. All 4 forms are closely linked to HLA and represent the effects of various combinations of alleles.
In female newborns, the external genitalia are masculinized; gonads and internal genitalia are normal. Postnatally, untreated males as well as females may manifest rapid growth, penile or clitoral enlargement, precocious adrenarche, and ultimately early epiphyseal closure and short stature. A mild form of late-onset adrenal hyperplasia due to 21-hydroxylase deficiency can occur in adults and has hirsutism as the only manifestation in the most attenuated form ... Presentation with gynecomastia and bilateral testicular masses was reported ... Kuttenn et al. (1985) found that 21-hydroxylase deficiency was the basis of hirsutism in 24 of 400 women (6%) ... In a follow-up study of 52 males with congenital virilizing adrenal hyperplasia seen at Johns Hopkins between 1950 and 1978, 51 had 21-hydroxylase deficiency and 1 had 11-hydroxylase deficiency ... women with classic CAH have relatively low fertility rates ... Patients with the HLA-Bw47 antigen invariably show simultaneous deficiencies of 21-hydroxylase activity and the C4A ... Speiser et al. (1992) correlated genotype and phenotype in 88 families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Mutations were detected on 95% of chromosomes examined ... Jones (1978) found cases of mild 'adult' adrenal hyperplasia manifest by oligomenorrhea and treated like the usual form with adrenocorticosteroids ... Congenital adrenal hyperplasia affects about 1 in 5,000 births ...
Adrenal Hyperplasia, Congenital, Due to 11 Beta - Hydroxylase Deficiency
Victor A. McKusick, OMIM, Johns Hopkins University, July 13, 2007
[for Professionals mainly]
Cytochrome P450, Subfamily; Adrenal Hyperplasia IV; 11 Beta - Hydroxylase Deficiency; Hypersensitive Form of Adrenal Hyperplasia; Steroid 11 - Beta - Hydroxylase; P450C11B1 Deficiency; Cytochrome P450, Subfamily XIB, Polypeptide ...
Gene Map Locus: 8q21 ... Hypertension is a feature that often distinguishes steroid 11-beta-hydroxylase deficiency from the 21-hydroxylase form of virilizing adrenal hyperplasia ... Since the block is at the final oxidation (dehydrogenation) of 18-hydroxycorticosterone to form aldosterone, the steroid pattern differs by an excess of the substance just proximal to the block. The genitalia are normal ...
Technical Report: Congenital Adrenal Hyperplasia (RE0027)
American Academy of Pediatrics; Volume 106, Number 6; December 2000, pp 1511-1518
[for Professionals mainly]
Congenital adrenal hyperplasia (CAH) consists of a family of disorders caused by reduced activity of enzymes required for cortisol biosynthesis in the adrenal cortex. The most common defect is 21-hydroxylase (21-OH) deficiency, which accounts for >90% of all cases of CAH. Classic 21-hydroxylase deficiency is found in about 1:12 000 to 1:15 000 births; the frequency of nonclassic deficiency is unknown, although it may occur in up to 3% of individuals in certain groups ... parental diagnosis and treatment: The objective of prenatal diagnosis and treatment of 21-OH deficiency is the prevention of prenatal virilization in affected female infants and the early recognition of the potential for salt wasting in the newborn infant ... Prenatal prediction of CAH attributable to classic 21-OH deficiency is possible by using a number of modalities ... The preferred technique for prenatal diagnosis is molecular genetic analysis using DNA extracted from chorionic villus cells or amniocytes for analysis of CYP21B, C4 and HLA class I and II genes ... Prenatal Treatment of CAH Attributable to 21-OH Deficiency; Prenatal treatment of CAH to prevent the virilization of an affected female fetus has been considered desirable by a number of investigators ... children aged 6 months to 5.5 years treated prenatally ... No significant differences in cognitive abilities or behavior problems were identified ... Maternal adverse effects of dexamethasone may be serious and long-lasting ... In a European survey, adverse effects occurred in approximately one third of women who were treated until delivery and for whom data were available.48 Marked weight gain, reported in approximately 25% ... Maternal treatment seems to prevent or reduce virilization in approximately 75% of affected female fetuses but has not been uniformly successful in all pregnancies ... Neonatal Screening: The major objectives of newborn screening for CAH attributable to 21-OH deficiency are to identify infants at risk for the development of life-threatening adrenal crisis and to prevent the incorrect male sex assignment of affected female infants with ambiguous genitalia ... Reliability of Screening Tests: The reliability of each screening program is based on evaluation of both the false-negative and false-positive rates. There have been extraordinarily few false-negative results in newborn screening worldwide.62 The majority of reported false-positive results have been caused by low birth weight and premature birth, in which the 17-OHP levels are invariably higher ...
Congenital Adrenal Hyperplasia: A Handbook For Parents
Jose L. Gonzalez, M.D, et al, Texas Department of Health
Your baby had a blood test shortly after birth to look for a number of inherited medical conditions which require early treatment. The screening test does not prove that your baby has CAH. More tests will be needed to prove its presence. It is important to have your child tested as soon as possible. Untreated CAH can result in serious illness and, in some cases, death ... Treatment: CAH is never "outgrown"; treatment is required for life ... Psychological Consideration: If your baby was born with abnormalities of the genitals you may wish to tell family and friends that your baby has a minor defect which will delay the doctors in being able to confirm the sex of the child for a few days. Reassure them that the baby is healthy and normal in every other way. You may wish to add that your baby has a hormone imbalance that will require treatment. Issues relating to sexuality may cause concerns which are difficult to talk about. Be reassured that the little girl with CAH will grow up to function as a normal woman. Likewise, be reassured that the little boy with CAH who is taking medication to prevent excessive adrenal male-type hormone is still making plenty of male hormone! ...
Congenital Adrenal Hyperplasia: Not Really a Zebra
Michael A. Deaton, PH.D., M.D, et al, American Family Physician, March 1, 1999
[for Professionals mainly] [Support Groups]
once considered a rare inherited disorder with severe manifestations. Mild congenital adrenal hyperplasia, however, is common, affecting one in 100 to 1,000 persons in the United States and frequently eluding diagnosis ... Even mild congenital adrenal hyperplasia can result in life-threatening sinus or pulmonary infections, orthostatic syncope, shortened stature and severe acne. Women with mild congenital adrenal hyperplasia often present with hirsutism, oligomenorrhea or infertility ... Classical congenital adrenal hyperplasia is rare, affecting only one in 14,000 patients, but mild forms of the disease may occur in one of every 100 to 1,000 persons ... Signs and Symptoms Suggesting Mild Congenital Adrenal Hyperplasia ... Children: Moderate to severe recurrent sinus or pulmonary infections; Severe acne; Hyperpigmentation, especially of the genitalia; Tall for age; Early onset of puberty. Adults : Childhood history as defined above;
Syncope or near-syncope; Shortened stature compared with either parent; Hypotension (21-hydroxylase deficiency); Hypertension (11-ß hydroxylase deficiency). Women :
Clitorimegaly; Poorly developed labia; Hirsutism; Infertility; Polycystic ovary syndrome ...
Adrenal Hyperplasia, Congenital, Due to 17-Alpha-Hydroxylase Deficiency
Victor A. McKusick, OMIM, Johns Hopkins University, January 29, 2008
Adrenal Hyperplasia V; 17 Alpha - Hydroxylase Deficiency;
Cytochrome P450, Subfamily XVII, Included;
Gene Map Locus: 10q24.3 ... Deficiency of adrenal 17-hydroxylation activity was first demonstrated in a single patient by Biglieri et al. (1966) ... Production of excessive corticosterone and deoxycorticosterone resulted in hypertension and hypokalemic alkalosis. Aldosterone synthesis was almost totally absent ... Human male sexual differentiation requires production of fetal testicular testosterone, whose biosynthesis requires steroid 17,20-lyase activity. The existence of true isolated 17,20-lyase deficiency has been questioned because 17-alpha-hydroxylase and 17,20-lyase activities are catalyzed by a single enzyme, microsomal cytochrome P450c17, and because combined deficiencies of both activities were found in a patient thought to have had isolated 17,20-lyase deficiency ...
Congenital Adrenal Hyperplasia
Washington State Department of Health, November 20, 2006
... screening for CAH (classical salt-wasting 21-hydroxylase deficiency) has proven to be of benefit for early identification and treatment of infants to prevent severe adrenal crisis, its sequelae, and progressive signs of androgen excess ... also proved beneficial in facilitating proper sex assignment ...
Last Updated: 2008/06/10