5-alpha reductase deficiency (5-alpha reductase deficiency) - Gen SRD5A2.
Deficiency of 5-alpha reductase is a disorder that affects male sexual development before birth and during puberty. People with this disease are genetically male, with X and Y chromosome in each cell, and testicles. However, the body does not produce enough of the hormone dihydrotestosterone (DHT). This hormone plays a critical role in male sexual development, and this hormone deficiency disrupts the formation of the external sex organs before birth.
Many people deficient in 5-alpha reductase born with female external genitalia. In other cases, the external genitalia are not clearly distinguishable if they are male or female (ambiguous genitalia). Some affected children have genitals that appear predominantly male, often with a micropenis and hypospadias. During puberty, people with this disorder develop some of the secondary sexual characteristics such as increased muscle mass, voice change and pubic hair development. The penis and scrotum enlarged. Unlike many men, people with deficiency of 5-alpha reductase do not develop much facial or body hair. Affected males are infertile.
This process is due to mutations in the SRD5A2 gene, located on the short arm of chromosome 2 (2p23). This gene encodes steroid 5-alpha reductase 2 enzyme involved in direct processing of androgens. Specifically, the enzyme is responsible for a chemical reaction that converts testosterone hormone to the more potent androgen, dihydrotestosterone (DHT) in male reproductive tissues. Testosterone and DHT are essential for the normal development of male sexual characteristics. Before birth, testosterone is responsible for the formation of internal male genitalia, including the epididymis and vas deferens and seminal vesicles. DHT directs the development of the external genitalia including penis and scrotum, and prostate gland. During puberty, these hormones also play an important role in the development of male secondary sexual characteristics, such as growth of facial and body hair, increased muscle mass, and deepening of the voice role.
Have identified at least 96 mutations in the SRD5A2 gene in individuals deficient 5-alpha reductase. The mutations described so far have been: missense mutations (70), and cutting mutations -splicing- connection (6), regulatory mutations (1), small deletions (13), small insertions (2), small insertions / deletions ( 2) and larger deletions (2). Mutations in the gene SRD5A2 prevent steroid 5-alpha reductase enzyme effectively converts 2 testosterone to DHT in reproductive tissues development. These factors underlying hormonal changes in male sexual development observed in newborns with deficiency of 5-alpha reductase. During puberty, the testes produce more testosterone. It is believed that persons deficient 5-alpha reductase developing secondary male sexual characteristics in response to higher concentrations of this hormone. Some affected also retain a small amount of 5-alpha reductase 2, which can produce DHT and contribute to development of secondary sexual characteristics during puberty.
This disease is inherited in 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. Although women may inherit mutations in both copies of the gene SRD5A2, sexual development is not affected. The development of female sex characteristics requires DHT, so that a lack of steroid 5-alpha reductase activity 2 does not cause physical changes to it. Only individuals who have mutations in both copies of the SRD5A2 gene and are genetically male (with an X and a Y chromosome in each cell) have the characteristic signs of deficiency 5-alpha reductase.
Tests in IVAMI: in IVAMI perform detection of mutations associated with deficiency of 5-alpha reductase by PCR amplification delos complete exons SRD5A2 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).