Hydroxylase deficiency 21- ...; Congenital adrenal hyperplasia deficiency 21-hydroxylase (21-hydroxylase deficiency, Congenital adrenal hyperplasia due to 21 hydroxylase deficiency) - Gen CYP21A2

Adrenal steroid is a complex process that are involved various enzymes that act on cholesterol coordinately determining glucocorticoid synthesis and mineralocorticoids. Congenital adrenal hyperplasia is a set of alterations of adrenal steroid that cause a decrease in the biosynthesis of cortisol causes a compensatory increase secretion corticotropic hormone (ACTH). Increasing the concentration of ACTH stimulates the biosynthesis of steroids, leading to an increased synthesis of those prior to the blockade steroids, ie those whose synthesis is not altered by the enzyme deficiencies cause congenital adrenal hyperplasia which cause a variety of clinical conditions dependent deficit cortisol and distal to the blocking hormones and excess hormones and metabolites proximal to the blocking.

They described three types of 21-hydroxylase deficiency. Two types are classic forms, known as the most serious scavenger classical salt form, which represents about 75% of cases, and the virilizing classical form. The third type is called non - conventional type. Both men and women, with classic forms of 21-hydroxylase deficiency often have a period of rapid growth early, but their final adult height is generally lower than that of other family members. In addition, affected individuals may have decreased fertility. Other characteristic features of classical forms may include hirsutism in women, irregular menstruation, ambiguous genitalia and male pattern baldness. In addition, newborns with the type of salt removal may have loss of appetite, weight loss, dehydration and vomiting. Meanwhile, women with no classic type of 21-hydroxylase deficiency have normal female genitalia. As women get older affected may exhibit hirsutism, male pattern baldness, irregular menstruation, and decreased fertility. Males with classic type may present a growth of premature beard and small testicles. Some individuals with this type of 21-hydroxylase deficiency have no symptoms of the disease.

Congenital adrenal hyperplasia is caused in 90% of cases by a deficiency of the enzyme 21-hydroxylase (21-OH), now called P450c2. The clinical manifestation deficit P450c21 is expressed by varying degrees of deficiency of cortisol and aldosterone, which induces the increase in ACTH levels and stimulation of adrenal steroid that due to enzymatic block drift androgen synthesis. In cases of absence of cytochrome function (classic loser salt form), individuals have salt loss crises and neonatal genital virilization, leading to genital ambiguity in female newborns. In other cases, the deficit is less severe and can manifest only by virilization (simple virilizing classic form) or, in the best cases, by late hyperandrogenism (non - classical form).

Deficiency P450c21 enzyme is produced as a result of numerous genetic alterations in the gene encoding, CYP21A2, located on the short arm of chromosome 6 (6p21.3). The 21-hydroxylase enzyme is part of the family of cytochrome P450 enzymes. This enzyme is found in the adrenal glands, which play a role in the production of cortisol and aldosterone. Cortisol has many functions, such as maintaining the levels of blood sugar, protecting the body from stress and suppressing inflammation. Aldosterone is sometimes called the salt - retaining hormone because it regulates the amount of salt retained by the kidneys. Salt retention affects concentrations of fluid in the body and blood pressure.

There are more than 100 mutations in the CYP21A2 gene responsible for 21-hydroxylase deficiency. Over 80% of cases conversions occurring gene inactivation, although any type of modification may be responsible for the condition. Other mutations change the amino acid 21-hydroxylase enzyme or deleted or inserted DNA fragments in the CYP21A2 gene. In most cases the losing classical salt form (40-70% depending on the population), individuals have the R357W and Q319X mutations, altered splicing (cutting and sealing) at the level of intron 2 or deletions partial or total gene. In individuals with virilizing form the most common alterations detected in clinical practice have been, among others, I173N and V282L. All types of 21-hydroxylase deficiency interferes with the production of cortisol and aldosterone. The substances commonly used to form these hormones accumulate in the adrenals and become androgen. Excessive production of androgens results in abnormalities of sexual development in people with 21-hydroxylase deficiency.

See Congenital Adrenal Hyperplasia caused by deficiency of 11-?-hydroxylase and Congenital Adrenal Hyperplasia caused by deficiency of 17-?-hydroxylase - - you can target diagnosis and enables the molecular characterization of the various ways in which congenital adrenal hyperplasia occurs rational genetic counseling of patients and relatives of the more severe forms of the disease. In addition, molecular and sequencing techniques allow prenatal genetic diagnosis by earliest methods, allowing earlier treatment and a better fit of individualized treatment necessary in any case to normalize the growth rate and other disturbances caused by this pathology. In fact, prenatal diagnosis can begin treatment before week 7 of gestation, in which differentiation of the external genitalia occurs, with a marked improvement in treatment efficiency.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with 21-hydroxylase deficiency, by complete PCR amplification of the exons of CYP21A2 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).