{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:24:57Z","timestamp":1787837097277,"version":"build-2784847793"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gitelman syndrome (GS) is a rare autosomal recessive salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. While typically presenting in adolescence or early adulthood, atypical presentations and delayed diagnoses into later adulthood pose significant clinical challenges. We report a case of a 60-year-old female who presented with generalized weakness, lethargy, and severe electrolyte abnormalities, including profound hyponatremia (109 mmol\/L), hypokalemia (2.91 mmol\/L), hypocalcemia (&lt;6.0 mg\/dL), and hypomagnesemia (0.6 mg\/dL). Laboratory investigations revealed metabolic alkalosis, hypochloremia, elevated parathyroid hormone (172.90 pg\/ml), and inappropriate renal potassium wasting. Urinary studies showed relative hypocalciuria in the context of severe hypocalcemia. Genetic testing revealed no pathogenic variants in the SLC12A3 gene typically associated with GS, though variants of uncertain significance were identified in SLC22A12 and VPS33B genes. Management included aggressive electrolyte replacement, spironolactone, and dietary modifications, resulting in clinical improvement despite incomplete normalization of electrolytes. This case illustrates the complex clinical spectrum of GS, highlighting the importance of considering this diagnosis in older adults with unexplained electrolyte abnormalities. The absence of confirmatory SLC12A3 mutations despite classic biochemical features supports emerging evidence of genetic heterogeneity in GS. This case emphasizes the value of clinical diagnosis when genetic confirmation is lacking and the effectiveness of targeted symptomatic management. GS should be considered in the differential diagnosis of electrolyte abnormalities across all age groups. A high index of clinical suspicion and characteristic biochemical profile can guide diagnosis and management even in the absence of confirmatory genetic findings.<\/jats:p>","DOI":"10.4103\/aam.aam_86_25","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T03:01:17Z","timestamp":1748833277000},"page":"691-694","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Gitelman Syndrome in the Sixth Decade: An Atypical Presentation with Severe Electrolyte Abnormalities and Genetic Heterogeneity"],"prefix":"10.4103","volume":"25","author":[{"given":"Sachin","family":"Shivnitwar","sequence":"first","affiliation":[{"name":"Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandesh S.","family":"Raut","sequence":"additional","affiliation":[{"name":"Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubhangi","family":"Kanitkar","sequence":"additional","affiliation":[{"name":"Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasad Chandrakant","family":"Bagare","sequence":"additional","affiliation":[{"name":"Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"R1-20260504","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.kint.2016.09.046","article-title":"Gitelman syndrome: Consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference","volume":"91","author":"Blanchard","year":"2017","journal-title":"Kidney Int"},{"key":"R2-20260504","first-page":"221","article-title":"A new familial disorder characterized by hypokalemia and hypomagnesemia","volume":"79","author":"Gitelman","year":"1966","journal-title":"Trans Assoc Am Physicians"},{"key":"R3-20260504","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/ng0196-24","article-title":"Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter","volume":"12","author":"Simon","year":"1996","journal-title":"Nat Genet"},{"key":"R4-20260504","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1681\/ASN.2010090907","article-title":"Spectrum of mutations in Gitelman syndrome","volume":"22","author":"Vargas-Poussou","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"R5-20260504","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1750-1172-3-22","article-title":"Gitelman syndrome","volume":"3","author":"Knoers","year":"2008","journal-title":"Orphanet J Rare Dis"},{"key":"R6-20260504","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s12020-011-9556-0","article-title":"Gitelman's syndrome: A pathophysiological and clinical update","volume":"41","author":"Nakhoul","year":"2012","journal-title":"Endocrine"},{"key":"R7-20260504","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1046\/j.1523-1755.2001.059002710.x","article-title":"Yale Gitelman's and Bartter's Syndrome Collaborative Study Group. Gitelman's syndrome revisited: An evaluation of symptoms and health-related quality of life","volume":"59","author":"Cruz","year":"2001","journal-title":"Kidney Int"},{"key":"R8-20260504","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ekir.2018.09.015","article-title":"Clinical and genetic characteristics in patients with Gitelman syndrome","volume":"4","author":"Fujimura","year":"2019","journal-title":"Kidney Int Rep"},{"key":"R9-20260504","doi-asserted-by":"crossref","first-page":"E1478","DOI":"10.1210\/jc.2012-1707","article-title":"Genotype, phenotype, and follow-up in Taiwanese patients with salt-losing tubulopathy associated with SLC12A3 mutation","volume":"97","author":"Tseng","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"R10-20260504","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1530\/EJE-11-0224","article-title":"Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome","volume":"165","author":"Balavoine","year":"2011","journal-title":"Eur J Endocrinol"},{"key":"R11-20260504","doi-asserted-by":"crossref","first-page":"1\u2196","DOI":"10.1074\/jbc.M201868200","article-title":"Protein kinase A-independent activation of ERK and H, K-ATPase by cAMP in native kidney cells: Role of Epac I","volume":"277","author":"Laroche-Joubert","year":"2002","journal-title":"J Biol Chem"},{"key":"R12-20260504","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/ndt\/gft400","article-title":"Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration","volume":"29","author":"Rodr\u00edguez-Ortiz","year":"2014","journal-title":"Nephrol Dial Transplant"},{"key":"R13-20260504","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00467-012-2297-3","article-title":"Renal phosphate handling in Gitelman syndrome \u2013The results of a case-control study","volume":"28","author":"Vigan\u00f2","year":"2013","journal-title":"Pediatr Nephrol"},{"key":"R14-20260504","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1681\/ASN.2006101095","article-title":"Transcriptional and functional analyses of SLC12A3 mutations: New clues for the pathogenesis of Gitelman syndrome","volume":"18","author":"Riveira-Munoz","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"R15-20260504","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1046\/j.1523-1755.2002.00467.x","article-title":"Electrocardiogram with prolonged QT interval in Gitelman disease","volume":"62","author":"Bettinelli","year":"2002","journal-title":"Kidney Int"}],"container-title":["Annals of African Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aam.aam_86_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:15:51Z","timestamp":1787836551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aam.aam_86_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/aam.aam_86_25","relation":{},"ISSN":["1596-3519","0975-5764"],"issn-type":[{"value":"1596-3519","type":"print"},{"value":"0975-5764","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]},"assertion":[{"value":"2025-03-20","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-21","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}