CASE REPORT article

Front. Pediatr.

Sec. Neonatology

Volume 13 - 2025 | doi: 10.3389/fped.2025.1550608

Type II Bartter syndrome with a novel KCNJ1 variant in a premature neonate presenting with features of salt-wasting congenital adrenal crisis and pseudo-hypoaldosteronism AUTHOR INFORMATION

Provisionally accepted
Heung Ching  TsuiHeung Ching Tsui1*Hua Tse  Timothy ChengHua Tse Timothy Cheng2Kai Yee  LamKai Yee Lam2Lai Ting  LeungLai Ting Leung2Ka Nam  AuKa Nam Au3Wai Yu  WongWai Yu Wong3Luen Yee  Sylvia SiuLuen Yee Sylvia Siu3Lap Ming  WongLap Ming Wong3
  • 1Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
  • 2Hong Kong Children's Hospital, Kowloon, Hong Kong, SAR China
  • 3Tuen Mun Hospital, Tuen Mun, Hong Kong, SAR China

The final, formatted version of the article will be published soon.

IntroductionBartter syndrome (BS) is a rare group of inherited renal tubulopathies. Diagnosis of BS type II is challenging in the neonatal period as its clinical findings and biochemical features may mimic that of adrenal crisis and pseudo-hypoaldosteronism (PHA) initially. Treatment should be instituted immediately for acute adrenal insufficiency as it is a medical emergency, then modified according to available investigation results and treatment response. Case presentation We describe a premature female neonate with an antenatal history of severe unexplained polyhydramnios, presented with features of adrenal crisis managed with hydrocortisone and fludrocortisone. Initial endocrine investigations excluded salt-wasting congenital adrenal hyperplasia (SW-CAH) and pointed to the diagnosis of PHA with hyperreninemic hyperaldosteronism. Hydrocortisone was gradually weaned off while fludrocortisone was continued for sodium retention effect. Hyperkalemia quickly transited into hypokalemia requiring high potassium requirement. Clinical and biochemical features of BS gradually evolved with polyuria, excessive weight loss, hypochloremic metabolic alkalosis and hypercalciuria at 1 week of age. Urgent trio whole exome sequencing (WES) subsequently confirmed the diagnosis of BS type II where compound heterozygous missense variants were identified in the KCNJ1 gene, one of which was a novel variant. Fludrocortisone was stopped and indomethacin was started with favorable outcomes. ConclusionThough hypokalemia is the key feature of BS, transient hyperkalemia can occur in the early neonatal period in BS type II. Antenatal history should be enquired thoroughly to look for presence of severe unexplained polyhydramnios. The diagnosis of BS type II should be considered if other biochemical features are present. Genetic tests are important to provide a definite diagnosis and guide subsequent management and genetic counselling.

Keywords: antenatal Bartter syndrome, Pseudohypoaldosteronism, Adrenal crisis, Genotypephenotype correlation, KCNJ1 gene, severe polyhydramnios

Received: 23 Dec 2024; Accepted: 03 Jun 2025.

Copyright: © 2025 Tsui, Cheng, Lam, Leung, Au, Wong, Siu and Wong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Heung Ching Tsui, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China

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