NEW YORK (Reuters Health) - Gain-of-function mutations in the V2 vasopressin receptor (V2R) lead to a condition resembling the syndrome of inappropriate antidiuretic hormone secretion (SIADH), according to two case reports in The New England Journal of Medicine for May 5th. Unlike SIADH, serum levels of arginine vasopressin, also known as antidiuretic hormone, are undetectable.
Dr. Stephen E. Gitelman, at the University of California at San Francisco, and colleagues recently treated two unrelated infants, ages 2.5 and 3 months, who had euvolemic hyponatremia, serum hypo-osmolality, and elevated urine osmolality and urine sodium concentrations. One presented with symptoms of irritability and the other with two generalized seizures.
Treatment with the osmotic agent urea resulted in increased urinary output and normalization of the serum sodium levels.
The syndrome appeared to be similar to SIADH, except that, as noted, serum levels of arginine vasopressin were undetectable. In typical SIADH, arginine vasopressin levels tend to be elevated, the authors explain.
DNA sequencing of the patients’ V2R gene identified missense mutations in codon 137, which was also identified in one of the mothers. A functional assay for V2R revealed that the receptor was constitutively active, explaining the patients’ undetectable arginine vasopressin levels (because V2R binds arginine vasopressin), hyponatremia and increased urine osmolality.
The authors named the condition “nephrogenic syndrome of inappropriate antidiuresis.”
Dr. Gitelman’s team notes that up to 20% of patients with SIADH have low to undetectable levels of arginine vasopressin. They suggest that these patients may have nephrogenic syndrome of inappropriate antidiuresis.
“In light of these findings, we suggest referring to all SIADH-like conditions as syndromes of inappropriate antidiuresis (SIAD) and that these two case reports constitute a subtype,” they write. Before a diagnosis of nephrogenic syndrome of inappropriate antidiuresis is finalized in any patient, they recommend that the V2R gene undergo sequencing.
“Elucidation of the exact mechanism underlying the activation of these mutant V2 receptors will undoubtedly be of great help in clarifying the relationships between the structure and function of the V2 receptor and possibly other G protein-coupled receptors,” Dr. Nine V. A. M. Knoers, a professor at Radboud University Nijmegen Medical Centre in the Netherlands, writes in a related editorial. “It may even guide the design of rational drugs for V2 receptor-associated disease.”
Source: N Engl J Med 2005;352:1847-1850,1884-1890. [ Google search on this article ]
MeSH Headings:Argipressin: Genetic Techniques: Membrane Proteins: Investigative Techniques: Receptors, Cell Surface: Receptors, Pituitary Hormone: Sequence Analysis: Sequence Analysis, DNA: Receptors, Vasopressin: Receptors, Neurotransmitter: Receptors, Peptide: Receptors, Neuropeptide: Mutation, Missense: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
