{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T23:44:05Z","timestamp":1782690245594,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mitochondrial carbonic anhydrase VA (CA\u2010VA) deficiency is a rare inherited metabolic disorder caused by biallelic variants of the\n                    <jats:italic>CA5A<\/jats:italic>\n                    gene. It presents with hyperammonemia, lactic acidosis, and ketonuria, with or without hypoglycemia. We report the long\u2010term follow\u2010up of the first two reported cases of CA\u2010VA deficiency: a 16\u2010year\u2010old female (case 1) and her 14\u2010year\u2010old brother (case 2), both of whom presented with neonatal hyperammonemic encephalopathy, hypoglycemia, elevated lactate, ketonuria, and compensated metabolic acidosis. The diagnosis was made in both cases through the TIDEX study, which identified a homozygous pathogenic variant in the\n                    <jats:italic>CA5A<\/jats:italic>\n                    gene (c.697T&gt;C, (p.Ser233Pro)). The clinical course of the index patient revealed three additional metabolic decompensation episodes (MDEs) triggered by intercurrent illnesses, with the last episode occurring at 8\u2009years of age, highlighting the unusual timing of her MDEs compared to previously reported cases. Case 2 remained metabolically stable without any additional MDEs. These episodes were successfully treated with parenteral dextrose, a single dose of enteral carglumic acid, and occasionally parenteral lipids. Management of intercurrent illness included a sick\u2010day formula high in carbohydrates and fats. Currently, both cases show normal growth, development, and neurological outcomes, suggesting a favorable prognosis, and in keeping with previously reported cases. Early diagnosis of CA\u2010VA deficiency allows prompt treatment and prevents severe complications. With proper management, long\u2010term outcomes are favorable, although severe and fatal outcomes have been reported. The impact on longevity needs to be assessed over longer durations. The development of consensus management for CA\u2010VA deficiency is warranted.\n                  <\/jats:p>","DOI":"10.1002\/jmd2.70102","type":"journal-article","created":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T22:51:30Z","timestamp":1782687090000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010Term Follow\u2010Up of Patients With Mitochondrial Carbonic Anhydrase\n                    <scp>VA<\/scp>\n                    Deficiency. A Case Report and Literature Review"],"prefix":"10.1002","volume":"67","author":[{"given":"Shaymaa","family":"Shurrab","sequence":"first","affiliation":[{"name":"Division of Genetics and Metabolics, Department of Pediatrics McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira","family":"Mobarak","sequence":"additional","affiliation":[{"name":"Division of Medical Biochemical Genetics, Department of Pediatrics Tanta University  Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Horvath","sequence":"additional","affiliation":[{"name":"Division of Biochemical Genetics, Department of Pediatrics, Faculty of Medicine University of British Columbia  Vancouver British Columbia Canada"},{"name":"Division of Biochemical Genetics, Department of Pediatrics British Columbia Children's Hospital  Vancouver British Columbia Canada"},{"name":"British Columbia Children's Hospital Research Institute  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Stocker\u2010Ipsiroglu","sequence":"additional","affiliation":[{"name":"Division of Biochemical Genetics, Department of Pediatrics, Faculty of Medicine University of British Columbia  Vancouver British Columbia Canada"},{"name":"Division of Biochemical Genetics, Department of Pediatrics British Columbia Children's Hospital  Vancouver British Columbia Canada"},{"name":"British Columbia Children's Hospital Research Institute  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"van Karnebeek","sequence":"additional","affiliation":[{"name":"British Columbia Children's Hospital Research Institute  Vancouver British Columbia Canada"},{"name":"Centre for Molecular Medicine and Therapeutics University of British Columbia  Vancouver Canada"},{"name":"Department of Pediatrics Amsterdam University Medical Center  Amsterdam the Netherlands"},{"name":"Department of Pediatrics Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"United for Metabolic Diseases  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-9136","authenticated-orcid":false,"given":"Ramona","family":"Salvarinova\u2010Zivkovic","sequence":"additional","affiliation":[{"name":"Division of Biochemical Genetics, Department of Pediatrics, Faculty of Medicine University of British Columbia  Vancouver British Columbia Canada"},{"name":"Division of Biochemical Genetics, Department of Pediatrics British Columbia Children's Hospital  Vancouver British Columbia Canada"},{"name":"British Columbia Children's Hospital Research Institute  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1146\/annurev.bi.64.070195.002111","article-title":"Human Carbonic Anhydrases and Carbonic Anhydrase Deficiencies","volume":"64","author":"Sly W. 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D.","year":"2014","journal-title":"American Journal of Human Genetics"},{"issue":"10","key":"e_1_2_13_5_1","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/gim.2015.201","article-title":"Defective Hepatic Bicarbonate Production due to Carbonic Anhydrase VA Deficiency Leads to Early\u2010Onset Life\u2010Threatening Metabolic Crisis","volume":"18","author":"Diez\u2010Fernandez C.","year":"2016","journal-title":"Genetics in Medicine"},{"issue":"3","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/s41436-019-0677-9","article-title":"Fatal Metabolic Decompensation in Carbonic Anhydrase VA Deficiency Despite Early Treatment and Control of Hyperammonemia","volume":"22","author":"Baertling F.","year":"2020","journal-title":"Genetics in Medicine"},{"issue":"7","key":"e_1_2_13_7_1","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.braindev.2020.04.007","article-title":"Mitochondrial Carbonic Anhydrase VA Deficiency in Three Indian Infants Manifesting Early Metabolic Crisis","volume":"42","author":"Konanki R.","year":"2020","journal-title":"Brain & Development"},{"issue":"10","key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1515\/jpem-2020-0117","article-title":"Carbonic Anhydrase VA Deficiency: A Very Rare Case of Hyperammonemic Encephalopathy","volume":"33","author":"Olgac A.","year":"2020","journal-title":"Journal of Pediatric Endocrinology & Metabolism"},{"issue":"1","key":"e_1_2_13_9_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/jmd2.12171","article-title":"Two Cases of Carbonic Anhydrase VA Deficiency\u2014An Ultrarare Metabolic Decompensation Syndrome Presenting With Hyperammonemia, Lactic Acidosis, Ketonuria, and Good Clinical Outcome","volume":"57","author":"Marwaha A.","year":"2021","journal-title":"JIMD Reports"},{"key":"e_1_2_13_10_1","first-page":"200","article-title":"Carbonic Anhydrase (CA\u2010VA) Deficiency: An Under Recognised Cause of Neonatal Hyperammonemia With Excellent Outcome on Proactive Management","volume":"107","author":"Ibrahim J.","year":"2022","journal-title":"Archives of Disease in Childhood"},{"issue":"11","key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1093\/clinchem\/hvab112","article-title":"Acute Hyperammonemia, Lactic Acidosis, and Ketoacidosis in a Developmentally Normal Child","volume":"67","author":"Miller M. 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American Journal of Neuroradiology"},{"issue":"1","key":"e_1_2_13_28_1","first-page":"187","article-title":"Carbonic Anhydrase VA Deficiency in a Neonate With Hyperammonaemia, Lactic Acidosis and Severe Ketoacidosis","volume":"44","author":"Kalliope D.","year":"2021","journal-title":"Journal of Inherited Metabolic Disease"},{"key":"e_1_2_13_29_1","volume-title":"Carbonic Anhydrase VA Deficiency","author":"Karnebeek C.","year":"1993"},{"issue":"1","key":"e_1_2_13_30_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00234-021-02819-3","article-title":"Clinical Applications of Diffusion\u2010Weighted Sequence in Brain Imaging: Beyond Stroke","volume":"64","author":"Gaddamanugu S.","year":"2022","journal-title":"Neuroradiology"},{"issue":"4","key":"e_1_2_13_31_1","doi-asserted-by":"crossref","DOI":"10.3390\/diagnostics12040861","article-title":"MR Neuroimaging in Pediatric Inborn Errors of Metabolism","volume":"12","author":"Lai L. 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