Résumé
Context: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD), the X-linked disease resulting from activating mutation of the vasopressin V2 receptor gene (AVPR2), is a recently described condition causative of episodes of hyponatremia in boys and male and female adults.
Objective: The objective of the study was the pathophysiological characterization of NSIAD.
Design: A family with NSIAD was identified and investigated for hyponatremic episodes and degrees of urine dilution defects. For the first time, the impact of the mutated V2R on aquaporin 2 (AQP2) excretion is reported.
Setting: The study was conducted at a referral center.
Patients: Five patients of seven carriers (two young brothers and their mother and her two sisters) were investigated together with age-matched controls.
Interventions: There were no interventions.
Results: In NSIAD patients, urinary AQP2 excretion occurred independently of concomitant vasopressin excretion and strongly correlated with urine osmolality, confirming direct AQP2 involvement in urine concentration. Water loading was followed by a very slow and incomplete elimination in the asymptomatic hemizygous boy with no suppression of AQP2 excretion and a delayed elimination in the heterozygous women because of an incomplete suppression of AQP2, and it induced hyponatremia in all NSIAD patients. Two hemizygous carriers presented with severe hyponatremia-induced seizures, and the repetition in one of them led to mental retardation.
Conclusions: Hyponatremia was a constant and characteristic aspect of the abnormal response to even mild water-loading tests in an asymptomatic hemizygous child as well as heterozygous adults. We confirm the phenotypic variability of NSIAD, a disease that should be regarded in pediatric intensive care units in presence of severe and/or recurrent hyponatremia, and also in adults, because carriers are prone to hyponatremia. (J Clin Endocrinol Metab 95: E37-E43, 2010)