Alpha-hydroxylase / 17,20 lyase deficiency 17 ..., (17 alpha-hydroxylase / 17, 20-lyase deficiency) - Gen CYP17A1.

Deficiency 17alpha-hydroxylase / 17,20 lyase is an alteration affecting the function of certain hormone - producing glands and the gonads and adrenal glands, so affected individuals have an imbalance of many hormones they occur in these glands. This deficiency is part of a group of disorders known as congenital adrenal hyperplasia, in which hormone production and maturation and sexual development is impaired. Hormonal imbalances lead to signs and symptoms of this process including hypertension, hypokalemia and abnormal sexual development.

Deficiency 17alpha-hydroxylase / 17,20 lyase has been classified into two forms: the complete form, which is the most serious, and partially, usually milder. Men and women are affected by alterations in sexual development differently. Women affected with the full form of the disease are born with normal female external genitalia; However, the internal reproductive organs, including the uterus and ovaries, may be underdeveloped, and do not develop secondary sexual characteristics such as breasts and pubic hair, and amenorrhea. Women with partial deficiency may have altered some secondary sexual characteristics such as menstruation is usually irregular or absent. Either of the two forms causes infertility.

For its part, affected individuals who are chromosomally male, problems with sexual development lead to abnormalities of the external genitalia. Those most affected are born with characteristically female external genitalia. However, because no internal female reproductive organs, these individuals have amenorrhea and no female secondary sexual characteristics develop. Although these individuals have testicles, they are located in the abdomen (undescended). In some cases, complete deficiency results in ambiguous genitalia. Males with partial deficiency often have abnormal male genitalia, as micropenis, hypospadias, bifid or scrotum. Like women, men deficient either complete or partial are also infertile.

This process is due to mutations in the CYP17A1 gene, located on the long arm of chromosome 10 (10q24.3), encodes a member of the family of cytochrome P450 enzymes. Like other cytochrome P450 CYP17A1 is involved in the synthesis of steroid hormones. This group includes hormones testosterone and estrogen, which are necessary for normal sexual development and reproduction; mineralocorticoids, which help regulate the balance of sodium and water in the body; and glucocorticoids, which are involved in the maintenance of glucose concentrations in the blood and regulating the body's response to stress. CYP17A1 enzyme performs two important reactions in the process of production of steroid hormones. On the one hand, it has activity 17alpha-hydroxylase, which is important for the production of glucocorticoids and sex hormones. This converts to 17-hidroxipregnanolona pregnanolone progesterone and 17-hydroxyprogesterone. These hormone precursors are further processed to produce glucocorticoids and sex hormones. Furthermore, CYP17A1 enzyme has lyase 17.20, activity is essential in the production of sex hormones. To do this, converts the 17-hidroxipregnanolona in dehydroepiandrosterone (DHEA).

They described tens of mutations in the CYP17A1 gene in individuals deficient 17alpha-hydroxylase / 17,20 lyase. Mutations associated with this alteration reduce or eliminate the activity both 17alpha-hydroxylase activity and 17,20 lyase. Reducing these activities leads to partial deficiency, while the total loss of these activities causes the most severe form of the disease known as complete deficiency. No 17?-hydroxylase activity, pregnanolone and progesterone are not converted into 17-hydroxypregnenolone or 17-hydroxyprogesterone, which alters glucocorticoid production. Instead of pregnanolone mineralocorticoid and progesterone are processed. An excess of these hormones that regulate sodium leads to hypertension and hypokalaemia. A loss of 17,20-lyase activity impairs the production of sex hormones.

This process is inherited as an autosomal recessive pattern, that is, 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 deficiency of 17alpha-hydroxylase / 17,20 lyase, by complete PCR amplification of the exons of CYP17A1 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).