Background: Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder of renal water handling, often presenting in early infancy with severe polyuria and hypernatremia. Differentiating CNDI from central diabetes insipidus (CDI) remains challenging, and delayed identification may result in inappropriate therapy, leading to adverse growth and neurodevelopmental outcomes. Case Presentation: We present the case of an 8-month-old male infant with a history of suspected CDI since birth. He was treated with desmopressin (dDAVP) without clinical benefit. The absence of the posterior pituitary bright spot at magnetic resonance imaging supported the CDI diagnosis. Considering persistent polyuria with recurrent episodes of hypernatremia and low urine osmolality, a diagnosis of CNDI was proposed, and plasma copeptin (CP) levels were determined. Measurement of CP showed markedly increased concentrations, suggesting renal tubular resistance to vasopressin. dDAVP therapy was discontinued and patient's management was adjusted to include hydrochlorothiazide therapy and a high-calorie diet restricted in sodium and protein. The patient showed progressive clinical improvement with reduction of polyuria and stabilization of serum sodium levels, although linear growth delay persisted. A final diagnosis of CNDI was confirmed by molecular analysis that identified rare compound heterozygous variants in the AQP2 gene, c.85G > A variant (maternal) and c.553C > G (paternal). Conclusions: This case highlights the diagnostic pitfalls of CNDI in infancy and underscores the pivotal role of early CP assessment and molecular genetic testing in distinguishing CNDI from CDI. Prompt recognition of CNDI is essential to avoid ineffective dDAVP therapy and to initiate a targeted multidisciplinary approach. Rare AQP2 mutations further expand the genotypic spectrum of CNDI and emphasize the need for heightened clinical awareness and early referral to specialized centers.
A Case of Misdiagnosed Pediatric Congenital Nephrogenic Diabetes Insipidus due to AQP2 Variants
Cassaro, Fabiola;Sbilordo, Serena;Marseglia, Lucia;Galletta, Karol;Granata, Francesca;Arena, Salvatore;Chimenz, Roberto
2026-01-01
Abstract
Background: Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder of renal water handling, often presenting in early infancy with severe polyuria and hypernatremia. Differentiating CNDI from central diabetes insipidus (CDI) remains challenging, and delayed identification may result in inappropriate therapy, leading to adverse growth and neurodevelopmental outcomes. Case Presentation: We present the case of an 8-month-old male infant with a history of suspected CDI since birth. He was treated with desmopressin (dDAVP) without clinical benefit. The absence of the posterior pituitary bright spot at magnetic resonance imaging supported the CDI diagnosis. Considering persistent polyuria with recurrent episodes of hypernatremia and low urine osmolality, a diagnosis of CNDI was proposed, and plasma copeptin (CP) levels were determined. Measurement of CP showed markedly increased concentrations, suggesting renal tubular resistance to vasopressin. dDAVP therapy was discontinued and patient's management was adjusted to include hydrochlorothiazide therapy and a high-calorie diet restricted in sodium and protein. The patient showed progressive clinical improvement with reduction of polyuria and stabilization of serum sodium levels, although linear growth delay persisted. A final diagnosis of CNDI was confirmed by molecular analysis that identified rare compound heterozygous variants in the AQP2 gene, c.85G > A variant (maternal) and c.553C > G (paternal). Conclusions: This case highlights the diagnostic pitfalls of CNDI in infancy and underscores the pivotal role of early CP assessment and molecular genetic testing in distinguishing CNDI from CDI. Prompt recognition of CNDI is essential to avoid ineffective dDAVP therapy and to initiate a targeted multidisciplinary approach. Rare AQP2 mutations further expand the genotypic spectrum of CNDI and emphasize the need for heightened clinical awareness and early referral to specialized centers.Pubblicazioni consigliate
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