Hypoplasia congenital adrenal; Congenital adrenal hypoplasia X - linked (hypoplasia congenita Adrenal; X-linked adrenal hypoplasia congenita) - Gen DAX1 (NROB1)
Congenital adrenal hypoplasia (AHC) is a serious disease with a high incidence of prenatal and neonatal death due to an alteration in the development of the adrenals during the embryonic period. One of the main symptoms of this process is the adrenal insufficiency, which occurs when the adrenal glands do not produce sufficient hormones. Adrenal insufficiency usually begins in infancy or childhood and can cause vomiting, difficulty feeding, dehydration, hypoglycemia and shock. If these complications are not treated, they often can be potentially fatal. In addition, affected males may also have a deficiency of male sex hormones, which leads to underdevelopment of reproductive tissues, cryptorchidism, delayed puberty and infertility. Together, these features are known as hypogonadotrophic hypogonadism. The onset and severity of these signs and symptoms can vary, even among affected members of the same family.
This process is due to mutations in DAX1 gene, also called NROB1, located on the short arm of the X chromosome (Xp21.3). This gene encodes a protein that plays an important role in the development and function of several endocrine tissues in the body. These tissues include the adrenal glands, two hormone - secreting glands in the brain (hypothalamus and pituitary), and gonads. Before birth, DAX1 protein helps regulate genes that direct the formation of these tissues. DAX1 also helps regulate the production of hormones in endocrine tissues after they have formed.
They described over 120 mutations in the gene DAX1 in patients with congenital adrenal hypoplasia form of X - linked Some of these genetic changes are deletions of all or part of the gene DAX1. Other mutations result encoding an abnormally short version of the protein amino acids DAX1 or change in a critical region of DAX1. Most mutations responsible for congenital adrenal hypoplasia X linked coding inhibit any functional DAX1 protein. Dax1 deficiency disrupts the normal development and function of endocrine tissues in the body. The main features of congenital adrenal hypoplasia develops when endocrine glands such as the adrenal glands, the hypothalamus, the pituitary or gonads do not produce adequate amounts of hormones.
Congenital adrenal hypoplasia (AHC) is inherited as a recessive X - linked pattern in males, who have only one X chromosome, an altered copy of the gene in each cell it is sufficient to express the disease. In females, having two X chromosomes, the mutation must be present in both copies of the gene for the disease is expressed. Males are affected by recessive X - linked disorders much more frequently than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome. In X - linked recessive inheritance, a woman with a mutated copy of the gene in each cell is called a carrier. You can pass the altered gene, but usually has no signs and symptoms of the disease. In rare cases, however, women who carry a mutation NR0B1 may exhibit signs of adrenal insufficiency or hypogonadotropic hypogonadism such as developing reproductive tissues, delayed puberty, and absence of menstruation.
Early diagnosis of congenital adrenal hypoplasia sequencing methods can generate a significant decrease in morbidity and the risk of death and ensures prompt initiation of hormone replacement. In addition, in cases of congenital adrenal hypoplasia clinical symptoms they are heterogeneous and adjacent to other diseases, so their diagnosis exclusively from them may not be sufficient to ensure prompt and proper management of the disease.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with congenital adrenal hypoplasia (AHC), by complete PCR amplification of the exons of the gene DAX1 (NROB1) 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).