Three Pediatric Patients with Congenital Nephrogenic Diabetes Insipidus due to <i>AVPR2</i> Nonsense Mutations and Different Clinical Manifestations: A Case Report

Abstract

Congenital nephrogenic diabetes insipidus (CNDI), a rare hereditary disorder, is characterized by the inability of the kidneys to concentrate urine in response to the antidiuretic hormone arginine vasopressin (AVP); as a result, large volumes of unconcentrated urine are excreted. In addition to the clinical manifestations of CNDI, such as dehydration and electrolyte disturbances (hypernatremia and hyperchloremia), developmental delay can result without prompt treatment. In approximately 90% of cases, CNDI is an X-linked disease caused by mutations in the arginine vasopressin receptor 2 (<i>AVPR2</i>) gene. In approximately 9% of cases, CNDI is an autosomal recessive disease caused by mutations in the water channel protein aquaporin 2 (<i>AQP2</i>), and 1% of cases are autosomal dominant. We report a case of CNDI caused by a novel <i>AVPR2</i> nonsense mutation, c.520C&gt;T (p.Q174X), and cases of siblings in another family who had a different <i>AVPR2</i> nonsense mutation, c.852G&gt;A (p.W284X). Both cases responded well to treatment with hydrochlorothiazide and spironolactone. If CNDI is suspected, especially in carriers and neonates, aggressive genetic testing and early treatment may alleviate growth disorders and prevent irreversible central nervous system disorders and developmental delay.