{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:38:58Z","timestamp":1785893938561,"version":"3.56.0"},"reference-count":48,"publisher":"Walter de Gruyter GmbH","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"j_jpem-2018-0538_s_999\"><jats:title id=\"d614445e11652\">Background<\/jats:title><jats:p>Type I pseudohypoaldosteronism (PHA1) is a rare condition characterised by profound salt wasting, hyperkalaemia and metabolic acidosis due to renal tubular resistance to aldosterone (PHA1a) or defective sodium epithelial channels (PHA1b or systemic PHA). Our aim was to review the clinical presentation related to the genotype in patients with PHA1.<\/jats:p><\/jats:sec><jats:sec id=\"j_jpem-2018-0538_s_998\"><jats:title id=\"d614445e11660\">Methods<\/jats:title><jats:p>A questionnaire-based cross-sectional survey was undertaken through the British Society of Paediatric Endocrinology and Diabetes (BSPED) examining the clinical presentation and management of patients with genetically confirmed PHA1. We also reviewed previously reported patients where genotypic and phenotypic information were reported.<\/jats:p><\/jats:sec><jats:sec id=\"j_jpem-2018-0538_s_997\"><jats:title id=\"d614445e11668\">Results<\/jats:title><jats:p>Genetic confirmation was made in 12 patients with PHA1; four had PHA1a, including one novel mutation in<jats:italic>NR3C2<\/jats:italic>; eight had PHA1b, including three with novel mutations in<jats:italic>SCNN1A<\/jats:italic>and one novel mutation in<jats:italic>SCNN1B.<\/jats:italic>It was impossible to differentiate between types of PHA1 from early clinical presentation or the biochemical and hormonal profile. Patients presenting with missense mutations of<jats:italic>SCNN1A<\/jats:italic>and<jats:italic>SCNN1B<\/jats:italic>had a less marked rise in serum aldosterone suggesting preservation in sodium epithelial channel function.<\/jats:p><\/jats:sec><jats:sec id=\"j_jpem-2018-0538_s_996\"><jats:title id=\"d614445e11691\">Conclusions<\/jats:title><jats:p>We advocate early genetic testing in patients with presumed PHA1, given the challenges in differentiating between patients with PHA1a and PHA1b. Clinical course differs between patients with<jats:italic>NR3C2<\/jats:italic>and<jats:italic>SCNN1A<\/jats:italic>mutations with a poorer prognosis in those with multisystem PHA. There were no obvious genotype-phenotype correlations between mutations on the same gene in our cohort and others, although a lower serum aldosterone may suggest a missense mutation in<jats:italic>SCNN1<\/jats:italic>in patients with PHA1b.<\/jats:p><\/jats:sec>","DOI":"10.1515\/jpem-2018-0538","type":"journal-article","created":{"date-parts":[[2019,7,14]],"date-time":"2019-07-14T05:58:48Z","timestamp":1563083928000},"page":"959-967","source":"Crossref","is-referenced-by-count":29,"title":["Phenotypic diversity and correlation with the genotypes of pseudohypoaldosteronism type 1"],"prefix":"10.1515","volume":"32","author":[{"given":"Jaya Sujatha","family":"Gopal-Kothandapani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpan B.","family":"Doshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kath","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Christian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talat","family":"Mushtaq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja","family":"Padidela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renuka","family":"Ramakrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Cheetham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Dimitri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","reference":[{"key":"ref231","first-page":"233","article-title":"Early death of two children with generalized pseudo hypoaldosteronism type 1","volume-title":"Pediatric Nephrology (Vol. 29, No. 9, pp. 1834)","year":"2014"},{"key":"ref461","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1172\/JCI6821","article-title":"Functional expression of a pseudohypoaldosteronism type I mutated epithelial Na+ channel lacking the pore-forming region of its \u03b1 subunit","volume":"104","year":"1999","journal-title":"J Clin Invest"},{"key":"ref441","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s13312-013-0070-8","article-title":"Pseudohypoaldosteronism type 1: management issues","volume":"50","year":"2013","journal-title":"Indian Pediatr"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/ng0396-248","article-title":"Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1","volume":"12","year":"1996","journal-title":"Nat Genet"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1007\/s00467-009-1285-8","article-title":"Transient type 1 pseudo-hypoaldosteronism: report on an eight-patient series and literature review","volume":"24","year":"2009","journal-title":"Pediatr Nephrol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/966","article-title":"Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I","volume":"19","year":"1998","journal-title":"Nat Genet"},{"key":"ref01","first-page":"597","article-title":"Pseudohypoaldosteronism types I and II: little more than a name in common","volume":"30","year":"2017","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref261","first-page":"597","article-title":"Pseudohypoaldosteronism types I and II: little more than a name in common","volume":"30","year":"2017","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s10157-010-0277-0","article-title":"Increased Na reabsorption via the Na\u2013Cl cotransporter in autosomal recessive pseudohypoaldosteronism","volume":"14","year":"2010","journal-title":"Clin Exp Nephrol"},{"key":"ref511","doi-asserted-by":"crossref","first-page":"E467","DOI":"10.1152\/ajpendo.00066.2011","article-title":"A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1","volume":"301","year":"2011","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"e65676","DOI":"10.1371\/journal.pone.0065676","article-title":"Novel mutations in the SCNN1A gene causing pseudohypoaldosteronism type 1","volume":"8","year":"2013","journal-title":"PLoS One"},{"key":"ref411","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1210\/jc.2006-1161","article-title":"Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1","volume":"91","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"ref471","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/ccr3.129","article-title":"Phenotypic variation of autosomal recessive pseudohypoaldosteronism type I: a case in point","volume":"2","year":"2014","journal-title":"Clin Case Rep"},{"key":"ref11","first-page":"130010","article-title":"Pseudohypoaldosteronism type 1: clinical features and management in infancy","volume":"2013","year":"2013","journal-title":"Endocrinol Diab Metab Case Rep"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1507\/endocrj.EJ12-0330","article-title":"Clinical and molecular analysis of six Japanese patients with a renal form of pseudohypoaldosteronism type 1","volume":"60","year":"2013","journal-title":"Endocr J"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/GIM.0b013e31816b5cae","article-title":"ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007","volume":"10","year":"2008","journal-title":"Genet Med"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1172\/JCI6821","article-title":"Functional expression of a pseudohypoaldosteronism type I mutated epithelial Na+ channel lacking the pore-forming region of its \u03b1 subunit","volume":"104","year":"1999","journal-title":"J Clin Invest"},{"key":"ref101","doi-asserted-by":"crossref","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","year":"2015","journal-title":"Genet Med"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s10157-010-0277-0","article-title":"Increased Na reabsorption via the Na\u2013Cl cotransporter in autosomal recessive pseudohypoaldosteronism","volume":"14","year":"2010","journal-title":"Clin Exp Nephrol"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/humu.20371","article-title":"Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism","volume":"28","year":"2007","journal-title":"Hum Mutat"},{"key":"ref21","first-page":"361","article-title":"Three cases of Gordon syndrome with dominant KLHL3 mutations","volume":"30","year":"2017","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1530\/EJE-12-1000","article-title":"Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1","volume":"168","year":"2013","journal-title":"Eur J Endocrinol"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/966","article-title":"Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I","volume":"19","year":"1998","journal-title":"Nat Genet"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s13312-013-0070-8","article-title":"Pseudohypoaldosteronism type 1: management issues","volume":"50","year":"2013","journal-title":"Indian Pediatr"},{"key":"ref391","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.mce.2011.04.023","article-title":"Aldosterone resistance: structural and functional considerations and new perspectives","volume":"350","year":"2012","journal-title":"Mol Cell Endocrinol"},{"key":"ref421","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1507\/endocrj.EJ12-0330","article-title":"Clinical and molecular analysis of six Japanese patients with a renal form of pseudohypoaldosteronism type 1","volume":"60","year":"2013","journal-title":"Endocr J"},{"key":"ref281","first-page":"361","article-title":"Three cases of Gordon syndrome with dominant KLHL3 mutations","volume":"30","year":"2017","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref451","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1007\/s00467-009-1285-8","article-title":"Transient type 1 pseudo-hypoaldosteronism: report on an eight-patient series and literature review","volume":"24","year":"2009","journal-title":"Pediatr Nephrol"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jsbmb.2008.06.013","article-title":"Renin-aldosterone response, urinary Na\/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes","volume":"111","year":"2008","journal-title":"J Steroid Biochem Mol Biol"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1210\/jc.2006-1161","article-title":"Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1","volume":"91","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"ref491","first-page":"233","article-title":"Early death of two children with generalized pseudo hypoaldosteronism type 1","volume-title":"Pediatric Nephrology (Vol. 29, No. 9, pp. 1834)","year":"2014"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"E467","DOI":"10.1152\/ajpendo.00066.2011","article-title":"A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1","volume":"301","year":"2011","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1530\/EJE-12-1000","article-title":"Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1","volume":"168","year":"2013","journal-title":"Eur J Endocrinol"},{"key":"ref361","doi-asserted-by":"crossref","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","year":"2015","journal-title":"Genet Med"},{"key":"ref501","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jsbmb.2008.06.013","article-title":"Renin-aldosterone response, urinary Na\/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes","volume":"111","year":"2008","journal-title":"J Steroid Biochem Mol Biol"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/GIM.0b013e31816b5cae","article-title":"ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007","volume":"10","year":"2008","journal-title":"Genet Med"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000224334","article-title":"Clinical and molecular features of type 1 pseudohypoaldosteronism","volume":"72","year":"2009","journal-title":"Horm Res"},{"key":"ref401","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000224334","article-title":"Clinical and molecular features of type 1 pseudohypoaldosteronism","volume":"72","year":"2009","journal-title":"Horm Res"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/ng0396-248","article-title":"Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1","volume":"12","year":"1996","journal-title":"Nat Genet"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"e65676","DOI":"10.1371\/journal.pone.0065676","article-title":"Novel mutations in the SCNN1A gene causing pseudohypoaldosteronism type 1","volume":"8","year":"2013","journal-title":"PLoS One"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/BF01213376","article-title":"The influence of sodium on growth in infancy","volume":"7","year":"1993","journal-title":"Pediatr Nephrol"},{"key":"ref61","first-page":"76","article-title":"Congenital pseudohypoaldosteronism presenting in utero with acute polyhydramnios","volume":"7","year":"1998","journal-title":"J Matern Fetal Med"},{"key":"ref481","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/BF01213376","article-title":"The influence of sodium on growth in infancy","volume":"7","year":"1993","journal-title":"Pediatr Nephrol"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/ccr3.129","article-title":"Phenotypic variation of autosomal recessive pseudohypoaldosteronism type I: a case in point","volume":"2","year":"2014","journal-title":"Clin Case Rep"},{"key":"ref321","first-page":"76","article-title":"Congenital pseudohypoaldosteronism presenting in utero with acute polyhydramnios","volume":"7","year":"1998","journal-title":"J Matern Fetal Med"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.mce.2011.04.023","article-title":"Aldosterone resistance: structural and functional considerations and new perspectives","volume":"350","year":"2012","journal-title":"Mol Cell Endocrinol"},{"key":"ref271","first-page":"130010","article-title":"Pseudohypoaldosteronism type 1: clinical features and management in infancy","volume":"2013","year":"2013","journal-title":"Endocrinol Diab Metab Case Rep"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/humu.20371","article-title":"Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism","volume":"28","year":"2007","journal-title":"Hum Mutat"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"link":[{"URL":"http:\/\/www.degruyter.com\/view\/j\/jpem.2019.32.issue-9\/jpem-2018-0538\/jpem-2018-0538.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2018-0538\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T21:31:01Z","timestamp":1663968661000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2018-0538\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,25]]},"references-count":48,"journal-issue":{"issue":"9"},"URL":"https:\/\/doi.org\/10.1515\/jpem-2018-0538","relation":{},"ISSN":["2191-0251","0334-018X"],"issn-type":[{"value":"2191-0251","type":"electronic"},{"value":"0334-018X","type":"print"}],"subject":[],"published":{"date-parts":[[2019,9,25]]}}}