Nephrogenic Diabetes Insipidus Health Article

Genetic profile

Genes are the blueprint for the human body that directs the development of cells and tissue. Mutations in some genes can cause genetic disorders such as inherited nephrogenic diabetes insipidus. Every cell in the body has 23 pairs of chromosomes, 22 pairs of which are called autosomes and contain two copies of individual genes. The 23rd pair of chromosomes is called the sex chromosome because it determines a person's sex. Men have an X and a Y chromosome while women have two X chromosomes. X-linked nephrogenic diabetes insipidus is caused by a defect in the vasopressin-2 receptor (AVPR2) gene in the X chromosome which renders the kidneys unreceptive to ADH.

Since inherited NDI is usually inherited as an X-linked condition, almost all persons with the disorder are male. Females have two X chromosomes, which means they have two copies of each gene. Males have only one X chromosome and one copy of each gene. If a male has an altered AVPR2 gene, he will have NDI. If a female has one altered gene, she will be a carrier and will be at risk to pass the altered gene on to her children. If her son inherits the altered gene, he will be affected. If her daughter inherits the affected gene, she will be a carrier like her mother. If her son does not inherit the altered gene, he will not be affected and will not pass the altered gene on to his children. If a daughter does not inherit the altered gene, she will not pass it on to her children. If an affected male has children, all of his daughters will be carriers but none of his sons will be affected.

Women who have the abnormal AVPR2 gene may have milder symptoms of NDI than males. This is because early in development, one X-chromosome in each cell of a female is "turned off" at random. If by chance a woman has more than half of the X chromosomes that carry the normal AVPR2 gene turned off, she may have mild symptoms of NDI. Approximately 90% of people with inherited NDI have it as a result of this X-linked gene.

The gene that produces aquaporin-2 (AQP2) can cause autosomal recessive and autosomal dominant NDI when altered. The AQP2 gene produces a protein that helps the kidneys reabsorb water into the body and concentrate urine. Since the AQP2 gene is carried on chromosome 12, a non-sex chromosome, it is carried in both males and females. Also, an abnormal AQP2 gene is recessive, meaning if only one of the person's two AQP2 genes is abnormal, it will not cause NDI. If both genes are abnormal, then that person will have NDI. A child born to a couple who are both carriers of autosomal recessive NDI has a 25% chance to be affected since the child is at risk to receive a copy of the altered gene from its mother and father. In autosomal dominant NDI, either parent may be affected and may pass the altered gene to the child. Also, only one altered gene is necessary to be present for the condition to manifest. Acquired NDI is not hereditary and can not be genetically passed on from parents to their offspring.

Demographics

In general, the various types of NDI appear to affect people regardless of age, race, or ethnicity. However, in X-linked NDI, the predominance of cases is among males. The exact number of people with NDI is not known. Estimates range from one in every 500,000 to five in every 100,000. In acquired NDI, one of the diseases that can cause it is sickle cell anemia, which occurs primarily in people of African descent.