Endocrine Abstracts

Introduction: Congenital nephrogenic diabetes insipidus (CNDI) is a rare genetic disorder characterized by the kidneys’ inability to respond to arginine vasopressin (AVP), resulting in profound polyuria and risk of hypernatremic dehydration in early infancy. Approximately 90% of cases are X-linked, caused by mutations in the AVPR2 gene, while a minority arise from autosomal mutations in the aquaporin-2 (AQP2) gene. Early diagnosis is critical, as untreated CNDI may result in severe dehydration, failure to thrive, and neurodevelopmental impairment. Despite typical laboratory findings of dilute polyuria and hypernatremia, distinguishing CNDI from central diabetes insipidus can be challenging, especially in the neonatal period. Management focuses on minimizing urinary water loss, correcting electrolyte disturbances, and ensuring adequate growth and development.

Case: We report a 4-month-old boy presenting with polyuria (6.5 mL/kg/h), poor weight gain (4.8 kg, <3rd centile), and length 64 cm. There was no significant family history. Laboratory evaluation revealed hypernatremia (serum sodium 152 mmol/l), low urine osmolality (149 mosm/kg), and urine specific gravity of 1.001. An initial trial of oral desmopressin produced no change in urine output or osmolality. Given the early onset, laboratory findings, and lack of desmopressin response, CNDI was suspected. Water deprivation testing was avoided due to the patient’s age and risk of dehydration. Genetic analysis identified a pathogenic hemizygous mutation in the AVPR2 gene. Management comprised hydrochlorothiazide therapy (2 mg/kg/day) resulting in normalization of serum sodium and a reduction in urine output to 1.9 mL/kg/h. However, the child developed hypokalaemia, prompting the addition of low-dose amiloride.

Discussion: CNDI is a diagnostic and therapeutic challenge in infants, with genetic analysis playing a pivotal role in definitive diagnosis. Early recognition is essential to prevent irreversible sequelae of chronic dehydration. The treatment involves a combination of thiazide diuretics, potassium-sparing diuretics, and dietary modification to minimize urinary losses and promote growth. In our case, prompt genetic confirmation allowed for early targeted therapy, leading to normalization of electrolytes, improved growth trajectory, and favourable outcome. Long-term monitoring for growth, neurological development, and renal function remains imperative given the risks of chronic kidney disease.