{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T19:39:28Z","timestamp":1789241968730,"version":"build-2803163510"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T00:00:00Z","timestamp":1720224000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2020-02200"],"award-info":[{"award-number":["2020-02200"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut and Alice Wallenberg Foundation","doi-asserted-by":"publisher","award":["2015.0320"],"award-info":[{"award-number":["2015.0320"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Inga-Britt and Arne Lundberg's Research Foundation"},{"name":"The Swedish Freemason's Foundation for Children's Welfare"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Genetic variants in SEC61A1 are associated with autosomal dominant tubulointerstitial kidney disease. SEC61A1 is a translocon in the endoplasmic reticulum membrane and variants affect biosynthesis of renin and uromodulin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A patient is described that presented at 1 year of age with failure-to-thrive, kidney failure (glomerular filtration rate, GFR, 18 ml\/min\/1.73m2), hyperkalemia and acidosis. Genetic evaluation was performed by whole genome sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The patient has a novel de novo heterozygous SEC61A1 variant, Phe458Val. Plasma renin was low or normal, aldosterone was low or undetectable and uromodulin was low. Kidney biopsy at 2 years exhibited subtle changes suggestive of tubular dysgenesis without tubulocystic or glomerulocystic lesions and with renin staining of the juxtaglomerular cells. The patient experienced extreme fatigue due to severe hypotension attributed to hypoaldosteronism and at 8 years of age fludrocortisone treatment was initiated with marked improvement in her well-being. Blood pressure and potassium normalized. Biopsy at 9 years showed extensive glomerulosclerosis and mild tubulointerstitial fibrosis, as well as tubular mitochondrial abnormalities, without specific diagnostic changes. Her GFR improved to 54 ml\/min\/1.73m2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>As the renin-angiotensin system promotes aldosterone release, and the patient had repeatedly undetectable aldosterone levels, the SEC61A1 variant presumably contributed to severe hypotension. Treatment with a mineralocorticoid had a beneficial effect and corrected the electrolyte and acid-base disorder. We suggest that the increased blood pressure hemodynamically improved the patient's kidney function.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ckj\/sfae213","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T08:00:45Z","timestamp":1720252845000},"source":"Crossref","is-referenced-by-count":3,"title":["Hypoaldosteronism due to a novel SEC61A1 variant successfully treated with fludrocortisone"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7220-7658","authenticated-orcid":false,"given":"Diana","family":"Karpman","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Clinical Sciences Lund, Lund University , Lund , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin L","family":"Lindstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sk\u00e5ne University Hospital and Regional Laboratories , Malm\u00f6 , 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