{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T19:45:57Z","timestamp":1777059957796,"version":"3.51.4"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Galilee Medical Center Research Fund"},{"DOI":"10.13039\/501100002744","name":"Bar-Ilan University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002744","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Nephrol"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder caused by bi-allelic genetic variants in the 4 hydroxy-2 oxoglutarate aldolase (<jats:italic>HOGA-1<\/jats:italic>) gene. We report the natural history of PH3 in a 16-patient cohort, 15 from a unique genetically isolated population.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This retrospective single-center study followed PH3 patients between 2003 and 2023 with demographic, clinical, radiographic, genetic, and biochemical parameters. Genetic population screening was performed in four villages to determine carrier frequency and identify couples at risk in a genetically isolated population.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Sixteen patients with biallelic (or homozygous) pathogenic variants (PV) in <jats:italic>HOGA-1<\/jats:italic> (c.944_946 del, c.119C\u2009&gt;\u2009A, c.208C\u2009&gt;\u2009T) were included in the study, 15 Druze and one Jewish, aged 0\u201363\u00a0years at diagnosis (4 adults and 12 pediatric patients). All symptomatic patients had clinical or imaging signs of nephrolithiasis. One developed chronic kidney disease (CKD) stage 5; biopsy showed focal mesangial sclerosis and chronic tubulo-interstitial changes with few oxalate deposits. Two other patients had CKD stage 2 (eGFR 87 and 74\u00a0mL\/min\/1.73\u00a0m<jats:sup>2<\/jats:sup>) upon their last visit. The remaining cohort showed preserved kidney function until the latest follow-up. Of 1167 healthy individuals screened, 90 carriers were found, a rate of 1:13 in the genetically unique cohort screened.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>A high prevalence of PH3 patients was found among a unique cohort, but probably still underdiagnosed due to relatively mild disease course. The carrier rate is high. There is no specific therapy for PH3, but early diagnosis can prevent redundant diagnostic efforts and provide early treatment for kidney stone disease. Even in our homogeneous cohort, kidney stone disease severity and CKD degree were variable, supporting a suspected contribution of yet unknown genetic or environmental factors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s00467-024-06536-w","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T15:35:20Z","timestamp":1730302520000},"page":"731-741","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Primary hyperoxaluria type 3: from infancy to adulthood in a genetically unique cohort"],"prefix":"10.1007","volume":"40","author":[{"given":"Michal","family":"Julius","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadas Shasha","family":"Lavsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Limor","family":"Kalfon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nehama Cohen","family":"Kfir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Herskovits","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irith","family":"Wiesmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0065-1922","authenticated-orcid":false,"given":"Tzipora C. 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No informed consent from patients was requested. (IRB#_05-02-2007_GMC).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Hadas Shasha Lavsky is a principal investigator of Alnylam Pharmaceuticals Illuminate A, B, and C studies and of Bayer Fiona and Fiona-OLE studies. The other authors have no conflict of interest to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}