[Diagnosis and follow-up of 2 cases of pediatric nephrogenic syndrome of inappropriate antidiuresis resulting from activating mutation in AVPR2 and literature review].

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.

[Chronic metabolic alkalosis in a newborn infant caused by congenital chloride diarrhea]. / Chronische, metabolische Alkalose bei einem Neugeborenen durch eine kongenitale Chloriddiarrhö.

The case of a female preterm infant (gestational age 36 weeks) is described, who presented with abdominal distension, diarrhoea, dehydration and metabolic alkalosis at the fifth day of life. After different diagnostic tests had been performed, congenital chloride diarrhoea was suspected and chloride supplementation was started. However, this diagnosis could not be confirmed, until the measurement of electrolytes in faeces had been improved. Then, we found the typically elevated fecal chloride concentration (130-153 mmol/l) which exceeded the sum of the fecal concentration of sodium (64-90 mmol/l) and potassium (28-35 mmol/l). The chloride supplementation was increased to 6 mmol/kg/d NaCl and 2 mmol/kg/d KCl. The most recent examination at the age of 1 year revealed the girl to be in good clinical condition, with normal growth and psychomotor-development and with no evidence of renal impairment.

[Pseudohypoaldosteronism--renal salt loss syndrome. Therapy and course exemplified by 2 siblings]. / Pseudohypoaldosteronismus--renales Salzverlustsyndrom. Therapie und Verlauf am Beispiel von zwei Geschwistern.

In 2 sibs pseudohypoaldosteronism was diagnosed by measurements of high serum aldosterone and elevated plasma renin activity. During their first week of life the first born girl, phenotypically normal, went through a severe salt-losing crisis with hyponatremia and hyperkalemia. Steroids given because of suspected congenital adrenal hyperplasia had no effect. High parenteral and later oral substitution of sodium normalized the serum electrolytes. The younger brother had milder symptoms. His salt-losing crisis developing during the first week of life was treated immediately with salt substitution. Both children developed normally with high oral sodium chloride supplementation, as regulated by the parents, using daily body weight measurements. Both children frequently suffer salt-losing crises, generally preceded by simple upper respiratory tract infections, which have to be treated in the hospital by infusion with a hyperosmolar sodium chloride solution.