ESPE Abstracts

Background: NSIAD is a rare genetic cause of hyponatremia, due to activating mutations in AVPR2 gene, encoding the Arginine Vasopressin Receptor Type 2, and located on Xq28. Of the fewer than 30 reported cases, most have been managed with fluid restriction and urea.

Objective and hypotheses: Illustration of the presentation of a family with this genetic abnormality and approach to management.

Method: The clinical, biochemical and genetic findings are presented.

Results: A previously healthy and developmentally normal 14 month old boy presented with hyponatraemic seizures following increased water intake the previous day. Repeated investigations were consistent with inappropriate antidiuresis (serum Na 114 mmol/L, serum K 3.7 mmol/L, urine sodium 51 mmol/L and urine osmolality 301 mmol/kg); but a vasopressin level associated with hyponatraemia (Na 127 mmol/l) was low (1.7 pmol/l). Thyroid and adrenal function and imaging of the head, chest and abdomen were normal. There was no evidence of intracerebral, respiratory or renal infection. The child was managed with water restriction and salt supplementation resulting in normal sodium levels over the following four months. Sequencing of the AVPR2 gene found that the child was hemizygous for a c.409C>T missense mutation which results in amino acid substitution p.Arg137Cys, previously described as causing NSIAD. Family history revealed hyponatraemic seizures in a maternal uncle as a child (serum Na 118 mmol/L, urine Na 146 mmol/L, urine osmolality 893 mmol/kg), consistent with X-linked inheritance. He had been misdiagnosed as having inappropriate ADH secretion secondary to seizure activity.

Conclusion: This case illustrates the importance of considering NSIAD in children with hyponatraemia, with unexplained SIAD. Treatment is possible with water restriction and salt supplementation and the long-term outcome is good.