{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T10:07:16Z","timestamp":1782727636872,"version":"3.54.5"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Carbonic anhydrase VA (CA\u2010VA) deficiency is a rare cause of hyperammonemia caused by biallelic mutations in <jats:italic>CA5A.<\/jats:italic> Most patients present with hyperammonemic encephalopathy in early infancy to early childhood, and patients usually have no further recurrence of hyperammonemia with a favorable outcome. This retrospective cohort study reports 18 patients with CA\u2010VA deficiency caused by homozygosity for a founder mutation, c.59G&gt;A p.(Trp20*) in <jats:italic>CA5A<\/jats:italic>. The reported patients show significant intrafamilial and interfamilial variability, and display atypical clinical features. Two adult patients were asymptomatic, 7\/18 patients had recurrent hyperammonemia, 7\/18 patients developed variable degree of developmental delay, 9\/11 patients had hyperCKemia, and 7\/18 patients had failure to thrive. Microcephaly was seen in three patients and one patient developed a metabolic stroke. The same variant had been reported already in a single South Asian patient presenting with neonatal hyperammonemic encephalopathy and subsequent development of seizures and developmental delay. This report highlights the limitations of current understanding of the pathomechanisms involved in this disorder, and calls for further evaluation of the possible role of genetic modifiers in this condition.<\/jats:p>","DOI":"10.1002\/jmd2.12426","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T09:34:35Z","timestamp":1715160875000},"page":"226-232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A founder mutation in <i>CA5A<\/i> causing intrafamilial and interfamilial phenotypic variability in a cohort of 18 patients with carbonic anhydrase <scp>VA<\/scp> deficiency"],"prefix":"10.1002","volume":"65","author":[{"given":"Khalid","family":"Al\u2010Thihli","sequence":"first","affiliation":[{"name":"Genetic &amp; Developmental Medicine Clinic, Department of Genetics Sultan Qaboos University Hospital  Muscat Oman"},{"name":"Genetics Department, College of Medicine and Health Sciences Sultan Qaboos University  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Al Hashmi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics the Royal Hospital  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaisha","family":"Al Balushi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics the Royal Hospital  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asila","family":"Al\u2010Habsi","sequence":"additional","affiliation":[{"name":"Department of Nursing Sultan Qaboos University Hospital  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiman","family":"Al\u2010Ajmi","sequence":"additional","affiliation":[{"name":"Department of Radiology and Molecular Imaging Sultan Qaboos University Hospital  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Al\u2010Jasmi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, College of Medicine and Health Sciences United Arab Emirates University  Al Ain United Arab Emirates"},{"name":"Department of Pediatrics Tawam Hospital  Al Ain United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6305-9718","authenticated-orcid":false,"given":"Fathiya","family":"Al\u2010Murshedi","sequence":"additional","affiliation":[{"name":"Genetic &amp; Developmental Medicine Clinic, Department of Genetics Sultan Qaboos University Hospital  Muscat Oman"},{"name":"Genetics Department, College of Medicine and Health Sciences Sultan Qaboos University  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.201"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem\u20102020\u20100117"},{"key":"e_1_2_12_4_1","volume-title":"Carbonic Anhydrase VA Deficiency","author":"Karnebeek C","year":"2015"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.01.006"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.1984.tb12380.x"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1096-0"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2020.04.007"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12171"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0677-9"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2022.100573"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12322"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(90)90040-4"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305805110"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.64.070195.002111"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2014.897328"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebcr.2014.09.001"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40064\u2010015\u20101057\u20109"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12125"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12426","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T06:34:46Z","timestamp":1720161286000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,8]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/jmd2.12426"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12426","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,8]]},"assertion":[{"value":"2024-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}