{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T08:56:07Z","timestamp":1773046567266,"version":"3.50.1"},"reference-count":15,"publisher":"Walter de Gruyter GmbH","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2025-0526_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Pseudohypoaldosteronism type 2 (PHA2) is a rare autosomal dominant electrolyte disorder characterized by hypertension, hyperkalemia, metabolic acidosis, and suppressed renin activity, usually with preserved renal function. Pathogenic variants in\n                      <jats:italic>WNK1, WNK4, KLHL3<\/jats:italic>\n                      , and\n                      <jats:italic>CUL3<\/jats:italic>\n                      have been identified, with\n                      <jats:italic>CUL3<\/jats:italic>\n                      mutations particularly associated with early-onset and severe phenotypes. Thiazide diuretics are effective in correcting both electrolyte imbalance and hypertension.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0526_abs_002\">\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report a pediatric patient with early-onset PHA2 caused by a\n                      <jats:italic>de novo<\/jats:italic>\n                      splice-site variant (c.1207-2A&gt;C) in the\n                      <jats:italic>CUL3<\/jats:italic>\n                      gene. The patient, first evaluated at 2\u00a0years and 7\u00a0months of age for recurrent vomiting, was found to have hyponatremia, hyperkalemia, and metabolic acidosis, initially treated with fludrocortisone. On referral, significant hypertension, hyperkalemia, and suppressed renin and aldosterone were observed. Initiation of low-dose thiazide therapy led to normalization of blood pressure and electrolytes. Long-term follow-up confirmed clinical stability, normal growth, and appropriate developmental milestones.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2025-0526_abs_003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Aldosterone pathway defects may be misdiagnosed during the initial clinical assessment. This underscores the importance of a comprehensive diagnostic approach incorporating biochemical profiling and genetic testing to ensure accurate identification. Next-generation sequencing has emerged as a valuable tool for establishing a definitive diagnosis, particularly in cases with aldosterone defects. Timely and accurate diagnosis of PHA2 is critical, as persistent metabolic acidosis and hypertension may lead to significant growth and developmental impairments in pediatric patients. Despite the potential severity of clinical manifestations associated with\n                      <jats:italic>CUL3<\/jats:italic>\n                      -related PHA2, it is noteworthy that treatment with thiazide diuretics alone can effectively restore electrolyte balance and support normal growth and development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2025-0526","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T15:54:12Z","timestamp":1765468452000},"page":"285-290","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic pitfalls in aldosterone defects: a 9-year follow-up of early-onset pseudohypoaldosteronism type 2"],"prefix":"10.1515","volume":"39","author":[{"given":"Mevra","family":"Cay","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology, Faculty of Medicine , \u00c7ukurova University , Adana , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ihsan","family":"Turan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Faculty of Medicine , \u00c7ukurova University , Adana , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahriye","family":"Atm\u0131s","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Faculty of Medicine , \u00c7ukurova University , Adana , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leman Damla","family":"Kotan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Faculty of Medicine , \u00c7ukurova University , Adana , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukriye Tugce","family":"Celebi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Faculty of Medicine , \u00c7ukurova University , Adana , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayse Merve","family":"Cimen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Faculty of Medicine , \u00c7ukurova University , Adana , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eda","family":"Mengen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Faculty of Medicine , \u00c7ukurova University , Adana , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aysun Karabay","family":"Bayaz\u0131t","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Faculty of Medicine , \u00c7ukurova University , Adana , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bilgin","family":"Yuksel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Faculty of Medicine , \u00c7ukurova University , Adana , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"2026030907573179954_j_jpem-2025-0526_ref_001","doi-asserted-by":"crossref","unstructured":"Boyden, LM, Choi, M, Choate, KA, Nelson-Williams, CJ, Farhi, A, Toka, HR, et al.. 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