Nephrogenic diabetes insipidus (Nephrogenic diabetes insipidus) - Genes AVPR2 or AQP2.
Nephrogenic diabetes insipidus is a disorder of water balance. The body normally balances fluid intake with liquid excretion in urine. However, people with nephrogenic diabetes insipidus have polyuria, which causes them to have polydipsia. Affected individuals can quickly become dehydrated if you do not drink enough water, especially in hot weather or when ill. Nephrogenic diabetes insipidus can be acquired or inherited. The acquired form is caused by certain medications and chronic diseases and can occur at any time during life. Due to hereditary genetic mutations, and their signs and symptoms usually appear in the first months of life.
Children with hereditary diabetes insipidus can eat poorly, have stunted growth, be irritable and present fever, diarrhea and vomiting. Recurrent episodes of dehydration can cause slow growth and delayed development. If you are not well treated alteration, over time can damage the bladder and kidneys which causes pain, infections and kidney failure. With proper treatment, people affected often have few complications and a normal life expectancy. Nephrogenic diabetes insipidus should not be confused with diabetes mellitus, which is much more common. Diabetes mellitus by high concentrations of blood glucose resulting from the lack of the hormone insulin or lack of sensitivity to this hormone is characterized. Although diabetes insipidus and diabetes mellitus have some characteristics in common, they are different diseases with different causes.
The inherited form of diabetes insipidus may be due to mutations in at least two genes. About 90% of all cases of hereditary diabetes insipidus insipidus result from mutations in the gene AVPR2. Most of the remaining 10% of cases are due to mutations in the gene AQP2. The acquired form of diabetes insipidus may be caused by chronic kidney disease, certain drugs (such as lithium), hypokalemia, hypercalcemia or obstruction of the urinary tract passages.
AVPR2 gene, located on the long arm of the X chromosome (Xq28), encodes a protein known as vasopressin V2 receptor. This receiver works in conjunction with a hormone called vasopressin or antidiuretic hormone (ADH) in the kidneys. The V2 vasopressin receptor is located in the collecting ducts, which are a series of small tubes reabsorb water kidneys to pass into the bloodstream. The interaction between ADH and vasopressin V2 receptor causes chemical reactions that control the water balance of the body. Fluid intake when a person is low or when you lose a lot of fluids, the body produces more ADH. This hormone binds to the vasopressin V2 receptor and directs the kidneys to concentrate urine reabsorbing some of the water returned to the bloodstream. When fluid intake is adequate, less ADH is available to interact with the V2 vasopressin receptor. At present, less water is reabsorbed into the bloodstream and urine is more diluted.
There are more than 200 mutations in the gene AVPR2 in people with diabetes insipidus. Most of these mutations cause protein vasopressin V2 receptor is misfolded in an incorrect dimensional-3 form. The misfolded protein is retained inside the cell, where it is unable to reach the cell surface to interact with ADH. Other less common mutations in the gene AVPR2 coding avoid any protein or vasopressin V2 receptor result in a version of the protein that reaches the cell surface, but can not associate with ADH. Without V2 vasopressin receptor functional, the kidneys are unable to respond to signals ADH. As a result, the collecting ducts not reabsorb water as they should and the body produces excessive amounts of urine. These problems with the water balance are characteristic of diabetes insipidus.
The AQP2 gene, located on the long arm of chromosome 12 (12q12-q13), encodes a protein called aquaporin 2. This protein is localized in kidney collecting ducts, where it forms a channel that transports water molecules through cell membranes. The aquaporin channel 2 plays an essential role in maintaining water balance in the body. Placing these channels it is controlled by the hormone vasopressin or antidiuretic hormone (ADH), encoded by the gene AVPR2 previously seen.
They have identified at least 40 mutations in the AQP2 gene in people with diabetes insipidus. Most of the mutations cause the aquaporin protein fold improperly 2-dimensional in form March 1st. The misfolded protein is retained inside the cell, which can not reach the cell membrane for the transport of water molecules, which causes the kidneys are unable to respond to signals ADH. As a result, the collecting ducts not reabsorb water as they should, and the body produces excessive amounts of urine. These problems with the water balance are characteristic of diabetes insipidus.
When nephrogenic diabetes insipidus is due to mutations in the gene AVPR2, it inherited an X - linked recessive pattern AVPR2 The gene is located on the X chromosome, one of the two sex chromosomes. In males, an altered copy of the gene in each cell is sufficient to cause disease. In women, a mutation must occur in both copies of the gene to cause the disorder. However, some women who have a single mutated copy of the gene AVPR2 have characteristics of diabetes insipidus including polyuria and polydipsia. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome. When nephrogenic diabetes insipidus is due to mutations in the gene AQP2, you can have a pattern or autosomal recessive inheritance, less frequently, an autosomal dominant inheritance. In the autosomal recessive both gene copies in each 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. In the autosomal dominant AQP2 a mutated copy of the gene in each cell is sufficient to lead to the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with diabetes insipidus, by complete PCR amplification of the exons of AVPR2 and AQP2, respectively, and subsequent sequencing genes.
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).