Infant Nephrogenic Diabetes Insipidus: Challenges Leading to Delayed Management

Nephrogenic diabetes insipidus (NDI) is a rare, potentially life-threatening renal tubular disorder characterized by a decreased ability to concentrate urine due to antidiuretic hormone (ADH) resistance, leading to significant free water loss. The congenital form, most often caused by X-linked mutations in the AVPR2 gene, typically presents in early infancy. Due to its rarity and nonspecific clinical features in young children, such as failure to thrive, vomiting, and excessive fluid intake, diagnostic delays are common, especially in centers with limited prior experience in managing NDI.

We report a case of a 17-month-old male infant presenting with severe hypernatremia, dehydration, vomiting, and failure to thrive. Initial clinical findings, a partial response to desmopressin, and absent neurohypophysis signaling on MRI suggested central diabetes insipidus (CDI), leading to a delay in the correct diagnosis. However, persistent polyuria, despite escalating desmopressin doses, prompted reconsideration. Genetic testing confirmed a pathogenic AVPR2 mutation (c.541C > T, p. Arg181Cys), establishing the diagnosis of congenital NDI. Therapeutic management included thiazide diuretics, NSAIDs, and dietary sodium restriction, resulting in slow and gradual clinical stabilization.

This case highlights several diagnostic challenges, such as misinterpreting partial desmopressin response and MRI results. It emphasizes the importance of systematic diagnostic algorithms for infants with polyuria and early genetic testing when clinical presentations lack clarity. We aim to share our clinical experience and the pitfalls encountered while managing a patient with NDI and contribute to earlier and more effective recognition and treatment of this rare condition, preventing the development of life-threatening complications.