Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Nephrogenic Diabetes Insipidus (NDI) [N25.1]

OMIM numbers: 304800, 300538 (AVPR2)

Dr. rer. nat. Karin Mayer

Scientific Background

Nephrogenic diabetes insipidus (NDI) is caused by a non-response of the renal tubuli to the antidiuretic hormone (ADH) - urine cannot be concentrated. Symptoms are polyuria, polydipsia, fever, obstipation, and acute hypernatriemic dehydratation after birth which can lead to neurological disorders. Untreated, children can have a daily urine volume of more than 10 liters. Too low osmolarity of urine cannot be treated with ADH. Prevalence in newborns is estimated to be 8.8 in 1,000,000 boys. Besides adequate water supply a diet low in salt, potassium and proteins is advisable. Administration of thiazide diuretics in combination with non-steroidal, anti-inflammatory drugs like amiloride and/or indometacin is useful. 

NDI has an X-linked inheritance in 90% of all cases. Mutations in the AVPR2 gene on Xq28 encoding vasopressin V2 receptor of ADH are causal for the disease. ADH increases the water permeability of the basolateral membrane of the renal tubule cells. More than 200 mutations in all 3 coding exons and the 3’-untranslated region of the AVPR2 gene have been reported so far. The X-linked type clinically only manifests in males, however some heterozygous female carriers do have mild symptoms of NDI due to variable X-inactivation. 95% of all mutations in X-linked NDI are covered by sequence analysis of the AVPR2 gene. 10% of all patients bear a mutation in the AQP2 gene which encodes aquaporin-2, a vasopressin-sensitive water channel of the renal tubuli. AQP2 mutations can both have an autosomal recessive (9%) and an autosomal dominant (1%) inheritance.