{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:24:21Z","timestamp":1786980261023,"version":"build-2736575974"},"reference-count":6,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100016003","name":"Istanbul University Cerrahpa\u015fa","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100016003","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Nephrol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Autosomal recessive proximal renal tubular acidosis (AR-pRTA) with ocular abnormalities is a rare syndrome caused by variants in the\n                    <jats:italic>SLC4A4<\/jats:italic>\n                    gene, which encodes Na\/HCO3 cotransporter (NBCe1). The syndrome primarily affects the kidneys, but also causes extra-renal manifestations. Pancreatic type NBCe1 is located at the basolateral membrane of the pancreatic ductal cells and together with CFTR chloride channel, it is involved in bicarbonate secretion. In vitro models have demonstrated that mutations in\u00a0the pancreatic type NBCe1 lead to a reduction in\u00a0pancreatic bicarbonate secretion. Although elevated amylase levels have been observed in some cases, there is no evidence of symptomatic pancreas involvement in children with AR-pRTA. This report presents the case of a seven-year-old girl with AR-pRTA and exocrine pancreatic insufficiency. This novel presentation with a novel mutation in\n                    <jats:italic>SLC4A4<\/jats:italic>\n                    expands the extra-renal involvement in this rare disease. We recommend that these children be screened for exocrine pancreatic insufficiency.\n                  <\/jats:p>","DOI":"10.1007\/s00467-025-06682-9","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T07:48:42Z","timestamp":1737964122000},"page":"2189-2192","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exocrine pancreatic insufficiency as an unusual extrarenal manifestation of proximal renal tubular acidosis associated with a novel SLC4A4 mutation"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8951-5145","authenticated-orcid":false,"given":"Berfin","family":"Hasturk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3658-8622","authenticated-orcid":false,"given":"Ayse","family":"Agbas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8310-4053","authenticated-orcid":false,"given":"Ozlem","family":"Akgun-Dogan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6097-657X","authenticated-orcid":false,"given":"Esra Karabag","family":"Yilmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2424-6959","authenticated-orcid":false,"given":"Seha","family":"Saygili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1927-7256","authenticated-orcid":false,"given":"\u00d6mer Faruk","family":"Be\u015fer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3420-9756","authenticated-orcid":false,"given":"Nur","family":"Canpolat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"6682_CR1","doi-asserted-by":"publisher","first-page":"C569","DOI":"10.1152\/ajpcell.00301.2017","volume":"314","author":"MD Parker","year":"2018","unstructured":"Parker MD (2018) Mouse models of SLC4-linked disorders of HCO(3)(-)-transporter dysfunction. Am J Physiol Cell Physiol 314:C569\u2013C588. https:\/\/doi.org\/10.1152\/ajpcell.00301.2017","journal-title":"Am J Physiol Cell Physiol"},{"key":"6682_CR2","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/15440","volume":"23","author":"T Igarashi","year":"1999","unstructured":"Igarashi T, Inatomi J, Sekine T, Cha SH, Kanai Y, Kunimi M, Tsukamoto K, Satoh H, Shimadzu M, Tozawa F, Mori T, Shiobara M, Seki G, Endou H (1999) Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities. Nat Genet 23:264\u2013266. https:\/\/doi.org\/10.1038\/15440","journal-title":"Nat Genet"},{"key":"6682_CR3","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/ki.2013.320","volume":"86","author":"JA Kari","year":"2014","unstructured":"Kari JA, El Desoky SM, Singh AK, Gari MA, Kleta R, Bockenhauer D (2014) The case | Renal tubular acidosis and eye findings. Kidney Int 86:217\u2013218. https:\/\/doi.org\/10.1038\/ki.2013.320","journal-title":"Kidney Int"},{"key":"6682_CR4","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1681\/ASN.2004080667","volume":"16","author":"S Horita","year":"2005","unstructured":"Horita S, Yamada H, Inatomi J, Moriyama N, Sekine T, Igarashi T, Endo Y, Dasouki M, Ekim M, Al-Gazali L, Shimadzu M, Seki G, Fujita T (2005) Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities. J Am Soc Nephrol 16:2270\u20132278. https:\/\/doi.org\/10.1681\/ASN.2004080667","journal-title":"J Am Soc Nephrol"},{"key":"6682_CR5","doi-asserted-by":"publisher","first-page":"C16","DOI":"10.1152\/ajpcell.1999.276.1.C16","volume":"276","author":"H Shumaker","year":"1999","unstructured":"Shumaker H, Amlal H, Frizzell R, Ulrich CD 2nd, Soleimani M (1999) CFTR drives Na+-nHCO-3 cotransport in pancreatic duct cells: a basis for defective HCO-3 secretion in CF. Am J Physiol 276:C16-25. https:\/\/doi.org\/10.1152\/ajpcell.1999.276.1.C16","journal-title":"Am J Physiol"},{"key":"6682_CR6","doi-asserted-by":"publisher","first-page":"C729","DOI":"10.1152\/ajpcell.00166.2002","volume":"284","author":"H Satoh","year":"2003","unstructured":"Satoh H, Moriyama N, Hara C, Yamada H, Horita S, Kunimi M, Tsukamoto K, Iso ON, Inatomi J, Kawakami H, Kudo A, Endou H, Igarashi T, Goto A, Fujita T, Seki G (2003) Localization of Na+-HCO-3 cotransporter (NBC-1) variants in rat and human pancreas. Am J Physiol Cell Physiol 284:C729-737. https:\/\/doi.org\/10.1152\/ajpcell.00166.2002","journal-title":"Am J Physiol Cell Physiol"}],"container-title":["Pediatric Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00467-025-06682-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00467-025-06682-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00467-025-06682-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T05:17:51Z","timestamp":1748323071000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00467-025-06682-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":6,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["6682"],"URL":"https:\/\/doi.org\/10.1007\/s00467-025-06682-9","relation":{},"ISSN":["0931-041X","1432-198X"],"issn-type":[{"value":"0931-041X","type":"print"},{"value":"1432-198X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,27]]},"assertion":[{"value":"20 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 January 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent was obtained from the parents to perform the genetic analysis and report the case. The study was conducted in accordance with all applicable ethical and legal rules concerning medical research involving human studies in the Declaration of Helsinki ethical statement.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}