Diabetes Insipidus (DI) is a failure of the kidneys to conserve water along with the production of copious amounts of dilute (insipid) urine, leading to dehydration and a persistent cycle of thirst, water drinking and frequent urination. This is to be differentiated from Diabetes Mellitus (DM), where the problem is an overflow of sugar into the urine from a high blood sugar concentration, overwhelming the kidneys and pulling water along with the formation of copious amounts of "sweet" urine. A simple urine test usually differentiates the two syndromes.
Water absorption in the kidneys take place in an area called the distal tubules under the control of the anti-diuretic hormone (ADH) called arginine vasopressin. This hormone is secreted by the thalamic region of the brain and stored in the posterior part of the pituitary gland in the brain for release. Its release is influenced by drastic drops in blood volume, as in a major hemorrhage, or by small changes in the concentration of blood flowing over certain receptors in the thalamus. The released hormone acts on the kidneys to increase water absorption and produce concentrated urine.
Classifications
This control system can fail either in the production of the arginine vasopressin in the brain or in the response to the released hormone at the kidney level. There are two main types of Diabetes Insipidus: acquired (brought on by disease or drugs) and genetic (passed on from generation to generation). A further classification is functional: central (pertaining to the hormone production in the brain and its release) or nephrogenic (pertaining to the response of the kidneys to the released hormones). There are two less common forms, called dipsogenic (a fault in the thirst center of the brain) and gestational (brought on by the peculiar situations in pregnancy).
Only the genetic variety can be transmitted as there is currently no known transmissible disease syndrome that is directly involved in Diabetes Insipidus.
Genetic transmission
The most common congenital DI is the X-linked Nephrogenic Diabetes Insipidus (NDI). A woman carrying the defective gene has a 50/50 chance of passing it on to her children. The male child will have a 50/50 chance of receiving the gene and developing NDI at birth or early in life. The female child will have a 50/50 chance of receiving the gene and becoming a carrier who may or may not develop the disease, more often a mild form and usually with a later onset. A man carrying the defective genes will pass it on to all his daughters, making them carriers who may or may not develop the illness. The sons of the man will be free of the genes. The defect in this case is in the recognition of the ADH at the kidney.
A second genetic NDI is the autosomal recessive variety, which equally affects sons and daughters. The carriers are usually free of the illness. It requires both parents to be carriers for a child to receive two defective genes and go on to develop the disease. This is extremely rare. The defect here is in the response to the recognized ADH.
Central Diabetic Insipidus has a very rare genetic variety called Familial Neurogenic Diabetes Insipidus, which is transmitted as autosomal dominant. It is so rare that it has been described in only 45 families in the whole world. In this situation, there is a 50 percent chance that every child of a carrier of this gene will have the condition. It will affect both male and female children equally. The defect here is synthesis of faulty ADH.
Outlook
The outlook for DI is quite good, with chances of a normal life in the hands of the right specialist, though there is currently no cure. Differentiating the various types is necessary for prognostication. Genetic screening will be necessary in the presence of a family history or in the absence of a known causative factor, particularly in the very young patients.
Genetic counseling prior to conception will also be necessary in the case of known carriers of the defective genes.
