Objective: To analyze the clinical and genetic features, as well as the treatment outcomes of two boys with
nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by gain-of-function mutations in the V2
vasopressin receptor gene (AVPR2). Methods: The clinical manifestations, genetic testing, therapeutic interventions and the outcomes of two boys with NSIAD hospitalized in the Department of Endocrinology, Beijing Children's Hospital in April 2019 were reported. A literature search with "
Nephrogenic syndrome of inappropriate antidiuresis" and "AVPR2 gene" as keywords was conducted at the China national knowledge infrastructure (CNKI), the Wanfang Data Knowledge Service Platform, PubMed and Springer Link up to May 2020. Relevant published articles were reviewed. Results: The two cases presented with chronic and severe
hyponatremia with hypo-osmolality, inappropriately elevated urinary osmolality and urinary
sodium levels. The onset age was 5.25-years and 2 months respectively. AVPR2 sequencing revealed a previously described hemizygous activating mutation (c.409C>T, p.R137C) in both of boys, each inherited the variant from their mother. Patient 1 limited fluid intake by himself in his daily life, intravenous and oral
sodium supplementations showed no significant increase of serum
sodium level. Oral
furosemide increased the serum
sodium level and maintained it within normal range. The serum
sodium and
potassium levels were in the normal range during the 1-year follow-up period with oral
furosemide. The serum
sodium level of Patient 2 increased with restricting fluid intake and with
salt supplementation. However, after he experienced respiratory
infection, the plasma
sodium level decreased. Subsequently, oral anti-
infection medicine and
furosemide were applied. The serum
sodium level increased two days later and remained at a normal range afterwards. The boy was 1 year old with normal growth. He stopped taking
furosemide after 4 months while taking 1 gram of
salt per day, the blood
sodium level maintained at normal range. Literature search identified no reports in Chinese journals, whereas 50 publications were found in English journals. A total of 30 NSIAD probands were reported and 16 of those (53%) had childhood onset, most presented with
seizures. The majority had a hotspot change at the
nucleotide position of 409 in AVPR2. Nine cases had an
amino acid change as R137C and five cases as R137L. Fluid restriction and oral
urea intake were main treatment options, no report so far was found with oral
furosemide treatment. Conclusions: NSIAD presented with
hyponatremia without any other specific presentations. Genetic testing for variants in AVPR2 is helpful for early diagnosis and timely treatment. The first two cases of oral
furosemide treatment were reported by the article which helped to maintain a normal serum
sodium level after limiting fluid intake and supplementing
sodium which showed limited effect.