{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:35:39Z","timestamp":1791041739555,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hyperkalemia is a rare but severe condition in young children and usually discovered as a result of hemolysis of the blood samples taken. However, patients with defects in either aldosterone biosynthesis or function can also present with hyperkalemia- as well hyponatremia-associated, and metabolic acidosis. It is a challenge to make an accurate diagnosis of these clinical conditions. We conducted this study to investigate the clinical and genetic features of aldosterone signaling defects associated hyperkalemia in young children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A retrospective review was conducted at the pediatric department of the First Affiliated Hospital of Guangxi Medical University from 2012 to 2022.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>47 patients with hyperkalemia were enrolled, of which 80.9% (<jats:italic>n<\/jats:italic>\u2009=\u200938) were diagnosed with primary hypoaldosteronism, including congenital adrenal hyperplasia due to 21-hydroxylase deficiency (<jats:italic>n<\/jats:italic>\u2009=\u200932), isolated hypoaldosteronism (<jats:italic>n<\/jats:italic>\u2009=\u20091) due to CYP11B2 gene mutation and Xp21 contiguous gene deletion syndrome (<jats:italic>n<\/jats:italic>\u2009=\u20091). Additionally, 4 patients were clinically-diagnosed with primary adrenal insufficiency. Nine patients were confirmed with aldosterone resistance, of which one child was diagnosed with pseudohypoaldosteronism (PHA) type 1 with a mutation in the NR3C2 gene and 3 children were identified with PHA type 2 due to novel mutations in either the CUL3 or KLHL3 genes. Five patients had PHA type 3 because of pathologies of either the urinary or intestinal tracts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The etiologies of infants with hyperkalemia associated with aldosterone defects were mostly due to primary hypoaldosteronism. An elevated plasma aldosterone level may be a useful biomarker for the diagnosis an aldosterone functional defect in patients presented with hyperkalemia. However, a normal plasma aldosterone level does rule out an aldosterone defect in either its biosynthesis or function, especially in young infants. Molecular genetic analyses can greatly help to clarify the complexity of disorders and can be used to confirm the diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2023.1092388","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T05:04:25Z","timestamp":1673845465000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Aldosterone defects in infants and young children with hyperkalemia: A single center retrospective study"],"prefix":"10.3389","volume":"11","author":[{"given":"Xu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanshu","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzi","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.phrs.2016.09.039","article-title":"Emergency management of severe hyperkalemia: guideline for best practice and opportunities for the future","volume":"113","author":"Rossignol","year":"2016","journal-title":"Pharmacol Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1007\/s00467-017-3635-2","article-title":"Potassium regulation in the neonate","volume":"32","author":"Bonilla-Felix","year":"2017","journal-title":"Pediatr Nephrol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1177\/0885066605278969","article-title":"Hyperkalemia: a review","volume":"20","author":"Evans","year":"2005","journal-title":"J Intensive Care Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3243","DOI":"10.1210\/jc.2004-0016","article-title":"Primary adrenal insufficiency in children: twenty years experience at the sainte-justine hospital, Montreal","volume":"90","author":"Perry","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1111\/cen.13603","article-title":"Molecular genetic studies in a case series of isolated hypoaldosteronism due to biosynthesis defects or aldosterone resistance","volume":"88","author":"Turan","year":"2018","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s12902-021-00811-9","article-title":"Aldosterone signaling defect in young infants: single-center report and review","volume":"21","author":"Wijaya","year":"2021","journal-title":"BMC Endocr Disord"},{"key":"B7","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.mce.2003.10.013","article-title":"Aldosterone synthase deficiency and related disorders","volume":"217","author":"White","year":"2004","journal-title":"Mol Cell Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1530\/eje.0.1390096","article-title":"Molecular genetic study in two patients with congenital hypoaldosteronism (types I and II) in relation to previously published hormonal studies","volume":"139","author":"Peter","year":"1998","journal-title":"Eur J Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1159\/000281404","article-title":"Hook effect: a pitfall leading to misdiagnosis of hypoaldosteronism in an infant with pseudohypoaldosteronism","volume":"74","author":"Akin","year":"2010","journal-title":"Horm Res Paediatr"},{"key":"B10","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/s0755-4982(04)98501-6","article-title":"Pseudohypoaldost\u00e9ronismes","volume":"33","author":"Vantyghem","year":"2004","journal-title":"Presse Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000224334","article-title":"Clinical and molecular features of type 1 pseudohypoaldosteronism","volume":"72","author":"Riepe","year":"2009","journal-title":"Horm Res"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1681\/ASN.2010050457","article-title":"Mechanisms of type I and type II pseudohypoaldosteronism","volume":"21","author":"Furgeson","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1161\/HYPERTENSIONAHA.113.02187","article-title":"Pseudohypoaldosteronism type II: history, arguments, answers, and still some questions","volume":"63","author":"Healy","year":"2014","journal-title":"Hypertension"},{"key":"B14","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/nature10814","article-title":"Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities","volume":"482","author":"Boyden","year":"2012","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1097\/MOP.0000000000000104","article-title":"Disorders of aldosterone synthesis, secretion, and cellular function","volume":"26","author":"Root","year":"2014","journal-title":"Curr Opin Pediatr"},{"key":"B16","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1159\/000363107","article-title":"Novel insight into etiology, diagnosis and management of primary adrenal insufficiency","volume":"82","author":"Malikova","year":"2014","journal-title":"Horm Res Paediatr"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1515\/jpem-2020-0239","article-title":"Aldosterone deficiency with a hormone profile mimicking pseudohypoaldosteronism","volume":"33","author":"Mart\u00edn-Rivada","year":"2020","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.3892\/mmr.2016.4906","article-title":"Novel mutations in the CYP11B2 gene causing aldosterone synthase deficiency","volume":"13","author":"Li","year":"2016","journal-title":"Mol Med Rep"},{"key":"B19","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1159\/000381563","article-title":"Hypercalciuria in familial hyperkalemia and hypertension with KLHL3 mutations","volume":"130","author":"Mayan","year":"2015","journal-title":"Nephron"},{"key":"B20","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1297\/cpe.25.127","article-title":"A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a KLHL3 mutation","volume":"25","author":"Mitani","year":"2016","journal-title":"Clin Pediatr Endocrinol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1007\/s00467-003-1104-6","article-title":"Reversible secondary pseudohypoaldosteronism","volume":"18","author":"Watanabe","year":"2003","journal-title":"Pediatr Nephrol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"773246","DOI":"10.3389\/fped.2021.773246","article-title":"Case report: newborns with pseudohypoaldosteronism secondary to excessive gastrointestinal losses through high output stoma","volume":"9","author":"Ou","year":"2021","journal-title":"Front Pediatr"},{"key":"B23","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1007\/BF03350891","article-title":"Transient pseudo-hypoaldosteronism following resection of the ileum: normal level of lymphocytic aldosterone receptors outside the acute phase","volume":"22","author":"Vantyghem","year":"1999","journal-title":"J Endocrinol Invest"},{"key":"B24","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1042\/cs0610407","article-title":"Water and electrolyte composition of urine and ileal fluid and its relationship to renin and aldosterone during dietary sodium deprivation in patients with ileostomies","volume":"61","author":"Moss","year":"1981","journal-title":"Clin Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"986","DOI":"10.3390\/genes10120986","article-title":"The molecular genetics of gordon syndrome","volume":"10","author":"Mabillard","year":"2019","journal-title":"Genes (Basel)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1159\/000521626","article-title":"A novel homozygous KLHL3 mutation as a cause of autosomal recessive pseudohypoaldosteronism type II diagnosed late in life","volume":"146","author":"Etges","year":"2022","journal-title":"Nephron"},{"key":"B27","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1007\/s40620-021-01083-1","article-title":"Genotype-phenotype correlation in Gordon's Syndrome: report of two cases carrying novel heterozygous mutations","volume":"35","author":"Anglani","year":"2022","journal-title":"J Nephrol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12902-021-00767-w","article-title":"A case report of pseudohypoaldosteronism type II with a homozygous KLHL3 variant accompanied by hyperthyroidism","volume":"21","author":"Zhang","year":"2021","journal-title":"BMC Endocr Disord"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1635413","DOI":"10.1155\/2020\/1635413","article-title":"Hypertension accompanied by hyperaldosteronism, hyperkalemia, and hyperchloremic acidosis: a case report and literature review","volume":"2020","author":"Yang","year":"2020","journal-title":"Case Rep Endocrinol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1177\/0009922820920938","article-title":"Novel KLHL3 variant in an infant with Gordon syndrome","volume":"59","author":"Doan","year":"2020","journal-title":"Clin Pediatr (Phila)"},{"key":"B31","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1515\/jpem-2016-0309","article-title":"Three cases of Gordon syndrome with dominant KLHL3 mutations","volume":"30","author":"Park","year":"2017","journal-title":"Pediatr Endocrinol Metab"},{"key":"B32","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1159\/000475825","article-title":"Familial hyperkalemia and hypertension (FHHt) and KLHL3: description of a family with a new recessive mutation (S553l) compared to a family with a dominant mutation, Q309R, with analysis of urinary sodium chloride cotransporter","volume":"137","author":"Kliuk-Ben Bassat","year":"2017","journal-title":"Nephron"},{"key":"B33","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1093\/qjmed\/hcw043","article-title":"A novel mutation in KLHL3 gene causes familial hyperkalemic hypertension","volume":"109","author":"Kelly","year":"2016","journal-title":"QJM"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1007\/s00431-016-2782-y","article-title":"Hyperkalemia in young children: blood pressure checked?","volume":"175","author":"Hollander","year":"2016","journal-title":"Eur J Pediatr"},{"key":"B35","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1007\/s40620-021-01083-1","article-title":"Genotype-phenotype correlation in Gordon's Syndrome: report of two cases carrying novel heterozygous mutations","volume":"35","author":"Anglani","year":"2022","journal-title":"J Nephrol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.15252\/emmm.201505444","article-title":"Characterisation of the Cullin-3 mutation that causes a severe form of familial hypertension and hyperkalaemia","volume":"7","author":"Schumacher","year":"2015","journal-title":"EMBO Mol Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/j.sbi.2010.08.010","article-title":"Structural assembly of cullin-RING ubiquitin ligase complexes","volume":"20","author":"Zimmerman","year":"2010","journal-title":"Curr Opin Struct Biol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/aur.2238","article-title":"Meta-Analyses support previous and novel autism candidate genes: outcomes of an unexplored Brazilian cohort","volume":"13","author":"da Silva Montenegro","year":"2020","journal-title":"Autism Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1161\/HYPERTENSIONAHA.121.17624","article-title":"Novel CUL3 variant causing familial hyperkalemic hypertension impairs regulation and function of ubiquitin ligase activity","volume":"79","author":"Chatrathi","year":"2022","journal-title":"Hypertension"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1097\/HJH.0000000000003117","article-title":"A case of novel mutation of Cullin 3 gene in pseudohypoaldosteronism type II","volume":"40","author":"Wang","year":"2022","journal-title":"J Hypertens"},{"key":"B42","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1515\/jpem-2021-0361","article-title":"Gordon syndrome caused by a CUL3 mutation in a patient with short stature in Korea: a case report","volume":"35","author":"Park","year":"2022","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B43","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1111\/nep.13752","article-title":"Familial cases of pseudohypoaldosteronism type II harboring a novel mutation in the Cullin 3 gene","volume":"25","author":"Nakano","year":"2020","journal-title":"Nephrology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/1471-2369-14-166","article-title":"A young child with pseudohypoaldosteronism type II by a mutation of Cullin 3","volume":"14","author":"Tsuji","year":"2013","journal-title":"BMC Nephrol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1007\/s00467-013-2496-6","article-title":"CUL3 Gene analysis enables early intervention for pediatric pseudohypoaldosteronism type II in infancy","volume":"28","author":"Osawa","year":"2013","journal-title":"Pediatr Nephrol"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2023.1092388\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T05:04:29Z","timestamp":1673845469000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2023.1092388\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,16]]},"references-count":45,"alternative-id":["10.3389\/fped.2023.1092388"],"URL":"https:\/\/doi.org\/10.3389\/fped.2023.1092388","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,16]]},"article-number":"1092388"}}