The natural history of untreated X-linked nephrogenic diabetes insipidus with mutation in the vasopressin V2 receptor gene

Nephrogenic diabetes insipidus (NDI) results from the kidneys' inability to concentrate urine. We describe a 6-month-old male with a history of poor weight gain who presented with an incidental finding of hypernatremia (155 mEq/L) during an episode of acute gastroenteritis. The arginine vasopressin (AVP) test, along with molecular analysis revealing the M272R mutation in the AVP receptor 2 (AVPR2) gene, confirmed the diagnosis of congenital NDI. Interestingly, this mutation was also identified in the patient's maternal grandfather, who had never been diagnosed or treated for NDI despite a history of polydipsia, polyuria, and evidence of chronic kidney disease (CKD), severe bilateral hydronephrosis, hypertension, and severe bladder dysfunction. Early intervention with hydrochlorothiazide in the infant resulted in a significant reduction in urinary output and improved growth. The untreated grandfather's case highlights the potential severity of untreated NDI and the benefits of timely therapeutic intervention. This report contributes to the limited long-term data on congenital NDI, emphasizing the critical role of early detection and consistent management in preventing severe complications such as CKD, hydronephrosis, and bladder dysfunction. Regular follow-up, including renal ultrasound and monitoring of renal function, is essential for effectively managing NDI and improving patient outcomes.