Nephrogenic syndrome of inappropriate antidiuresis - An ethnically, genetically and phenotypically diverse disorder: First report in a Chinese adult and review of published cases

Abstract

Background: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare inherited disorder characterised by hyponatraemia. To date, most reported cases are Caucasians with gain-of-function variants in AVPR2, an X-linked gene which encodes the vasopressin V2 receptor (V2R). Recently, germline gain-of-function variants in the stimulatory G protein α-subunit (Gsα) were reported to cause dominantly inherited NSIAD.

Case report: We report the first Chinese adult diagnosed with NSIAD. He was found to be hemizygous for R137C-V2R, the most prevalent pathogenic variant among Caucasians. After the genetic diagnosis and counselling on the importance of fluid restriction, he had no recurrence of hyponatraemia to date.

Literature review: Case reports of NSIAD published in the English literature in PubMed were reviewed to summarise the genetic and phenotypic heterogeneity of this disorder.

Conclusion: NSIAD is ethnically, genetically and phenotypically diverse. The diagnosis should especially be considered in young patients with otherwise unexplained hyponatraemia. Target analysis of R137C-V2R should make the diagnosis in most cases. Genetic testing could confirm the diagnosis, motivate adherence to treatment, offer the possibility of genotype-guided therapy, and allow cascade screening to prevent hyponatraemia.

Keywords: AVPR2; Gsα; Hyponatraemia; Nephrogenic syndrome of inappropriate antidiuresis; V2R.