The following information may help to address your question:
What causes nephrogenic diabetes insipidus?
Nephrogenic diabetes insipidus can be either acquired or hereditary. The acquired form can result from chronic
kidney disease, certain medications (such as lithium), low levels of potassium in the blood (hypokalemia), high levels of calcium in the blood (hypercalcemia), or an obstruction of the urinary tract. Acquired nephrogenic diabetes insipidus can occur at any time during life.
[1]
The hereditary form of nephrogenic diabetes insipidus is caused by genetic
mutations, and its signs and symptoms usually become apparent within the first few months of life.
[1] The disease may be caused by mutations in two
genes,
AVPR2 (about 90% of cases)
and
AQP2 (about 10% of cases).
[1][2]
Last updated: 12/23/2016
What genes play a role in nephrogenic diabetes insipidus?
The hereditary form of nephrogenic diabetes insipidus can be caused by mutations in at least two genes. About 90 percent of all cases of hereditary nephrogenic diabetes insipidus result from mutations in the
AVPR2 gene. Most of the remaining 10 percent of cases are caused by mutations in the
AQP2 gene. Both of these genes provide instructions for making
proteins that help determine how much water is excreted in urine.
[1]
Last updated: 7/31/2011
How is nephrogenic diabetes insipidus inherited?
When nephrogenic diabetes insipidus results from mutations in the
AVPR2 gene (about 90% of the
inherited cases of nephrogenic diabetes insipidus) the condition has an
X-linked recessive pattern of inheritance.
[2] The
AVPR2 gene is located on the
X chromosome, which is one of the two
sex chromosomes. In males (who have only one X
chromosome), one altered copy of the gene in each
cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation usually has to occur in both copies of the gene to cause the disorder. However, some females who carry a single mutated copy of the
AVPR2 gene have features of nephrogenic diabetes insipidus, including
polyuria and
polydipsia. A characteristic of
X-linked inheritance is that fathers cannot pass X-linked
traits to their sons.
[1]
When nephrogenic diabetes insipidus is caused by mutations in the AQP2 gene (about 10% of the inherited cases of nephrogenic diabetes insipidus), it can have either an autosomal recessive or, less commonly, an autosomal dominant pattern of inheritance.[2] In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In autosomal dominant inheritance, one mutated copy of the AQP2 gene in each cell is sufficient to cause the disorder.[1]
Last updated: 12/23/2016
Is genetic testing available for nephrogenic diabetes insipidus?
Yes.
GeneTests lists laboratories offering clinical
genetic testing for both
X-linked and
autosomal types of nephrogenic diabetes insipidus. Clinical genetic tests are ordered to help diagnose a person or family and to aid in decisions regarding medical care or reproductive issues. Talk to your health care provider or a
genetic professional to learn more about your testing options.
Last updated: 7/31/2011
What if my son's genetic testing comes back normal?
If your son does not have a mutation in the
AVPR2 or
AQP2 genes, his condition may be due to another underlying cause. A careful evaluation should be done to rule out chronic renal insufficiency,
lithium toxicity,
hypercalcemia,
hypokalemia, and/or obstructions in the urinary tract.
[1][3]
Last updated: 7/31/2011
How might nephrogenic diabetes insipidus be treated?
Management is usually best accomplished by a team of physicians and other healthcare professionals. The team may include a
nutritionist, a pediatric (or adult)
nephrologist or
endocrinologist, and a clinical
geneticist.
[2]
The basis of management involves free access to drinking water and toilet facilities. The polyuria can be lowered with a low-salt (sodium), low-protein diet; thiazide diuretics: hydrochlorothiazide and chlorothiazide; other diuretics (i.e., potassium-sparing diuretic amiloride); and nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin. In babies, early recognition is very important because treatment can avoid the physical and intellectual disability that results from repeated episodes of dehydration and high levels of sodium (hypernatremia). Infants and very young children should be offered water every two hours during the day and night. In severe cases, continuous gastric feeding may be required. In adults, the decision to treat is based upon the individual patient's intolerance of the polyuria and polydipsia since, in almost all patients, the thirst mechanism is sufficient to maintain the sodium in the high-normal range. The medication desmopressin may be tried in patients who have persistent symptomatic polyuria after having the above described regimen. Several new approaches to treatment of this disorder are being investigated: V2 receptor chaperones and V2 receptor bypass.[2][4]
Last updated: 12/23/2016
Will my son need to take medication to treat nephrogenic diabetes insipidus for the rest of his life?
This depends of the underlying cause of your son's condition. If the condition is due to a certain medication, stopping the medicine may improve symptoms. This decision needs to be made with the help of a physician. Nephrogenic diabetes insipidus that is present at birth or is due to an inherited mutation is a chronic condition requiring lifelong treatment.
[5]
Last updated: 7/31/2011
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GARD Information Specialist
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