ArticleAmerican journal of human genetics2014
Mitochondrial carbonic anhydrase VA deficiency resulting from CA5A alterations presents with hyperammonemia in early childhood.
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Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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54citing papers in PubMed, 2 pooled it
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature.Orphanet journal of rare diseases · 2020Pooled it
- The hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.Orphanet journal of rare diseases · 2015Pooled it
- Long-Term Follow-Up of Patients With Mitochondrial Carbonic Anhydrase VA Deficiency. A Case Report and Literature Review.JIMD reports · 2026Article
- Article
- Mitochondrial β-carbonic anhydrase is a conserved metabolic rheostat for branched-chain amino acid catabolism and metabolic flexibility.The New phytologist · 2026Article
- Antenatal and Neonatal Management of Siblings With Carbonic Anhydrase VA Deficiency.JIMD reports · 2026Article
- A novel homozygous CA5A gene deletion in carbonic anhydrase VA deficiency presenting as developmental delay without metabolic crisis.Molecular genetics and metabolism reports · 2026Article
- Carbonic anhydrase VA deficiency due to a novelMolecular genetics and metabolism reports · 2025Article
- Hypocitrullinemia as an Early Diagnostic Biomarker for MT-ATP6 Mitochondrial Diseases.Journal of molecular neuroscience : MN · 2025Article
- Beyond Ornithine Metabolism in Gyrate Atrophy: Tissue-Specific Proteomic Insights into Neonatal and Adult OAT Deficiency.bioRxiv : the preprint server for biology · 2025Article
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- Urea cycle defects in adulthood: clinical presentation, diagnosis and treatment in genetically encoded hepatic metabolic disorders with a potential for encephalopathy.Metabolic brain disease · 2025Review
- Quo vadis ureagenesis disorders? A journey from 90 years ago into the future.Journal of inherited metabolic disease · 2024Review
- Enzyme Inhibitors as Multifaceted Tools in Medicine and Agriculture.Molecules (Basel, Switzerland) · 2024Review
- A founder mutation inJIMD reports · 2024Article
- Consequences of COVID-19 on Adipose Tissue Signatures.International journal of molecular sciences · 2024Article
- New isoxazolidinyl-basedJournal of enzyme inhibition and medicinal chemistry · 2023Article
- Fluconazole-Induced Protein Changes in Osteogenic and Immune Metabolic Pathways of Dental Pulp Mesenchymal Stem Cells of Osteopetrosis Patients.International journal of molecular sciences · 2023Article
- Mitochondrial carbonic anhydrase VA and VB: properties and roles in health and disease.The Journal of physiology · 2023Review
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Authors and funding
26 authors at 6 institutions in 4 countries.
Clara D van KarnebeekDivision of Biochemical Diseases, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Treatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada. Electronic address: cvankarnebeek@cw.bc.ca.
William S SlyDepartment of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, MO 63104, USA.
Colin J RossDepartment of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Treatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
Ramona SalvarinovaDivision of Biochemical Diseases, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Treatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
Joy Yaplito-LeeMetabolic Genetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia.
Saikat SantraDepartment of Clinical Inherited Metabolic Disorders, Birmingham Children's Hospital, Birmingham B4 6NH, UK.
Casper ShyrTreatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Gabriella A HorvathDivision of Biochemical Diseases, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Treatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
Patrice EydouxTreatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada; Department of Pathology & Laboratory Medicine, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Anna M LehmanTreatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Virginie BernardTreatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Theresa NewloveTreatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Department of Psychology, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Henry UkpehDepartment of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada.
Anupam ChakrapaniDepartment of Clinical Inherited Metabolic Disorders, Birmingham Children's Hospital, Birmingham B4 6NH, UK.
Mary Anne PreeceDepartment of Newborn Screening and Biochemical Genetics, Birmingham Children's Hospital, Birmingham B4 6NH, UK.
Sarah BallDepartment of Newborn Screening and Biochemical Genetics, Birmingham Children's Hospital, Birmingham B4 6NH, UK.
James PittMetabolic Genetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC 3010, Australia.
Hilary D VallanceTreatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Biochemical Genetics Laboratory, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada; Department of Pathology & Laboratory Medicine, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Marion Coulter-MackieDepartment of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Treatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
Hien NguyenDepartment of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, MO 63104, USA.
Lin-Hua ZhangDepartment of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Treatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
Amit P BhavsarTreatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Graham SinclairTreatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Biochemical Genetics Laboratory, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada; Department of Pathology & Laboratory Medicine, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Abdul WaheedDepartment of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, MO 63104, USA.
Wyeth W WassermanTreatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada; Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Sylvia Stockler-IpsirogluDivision of Biochemical Diseases, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Treatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
BC Children's Hospital · CABirmingham Children's Hospital · GBUniversity of British Columbia · CAChild and Family Research Institute · CASaint Louis University · USRoyal Children's Hospital · AU
Funding
BIOCHEMICAL GENETICS OF CARBONIC ANHYDRASE DEFICIENCIESR01DK040163 · NIDDK · SAINT LOUIS UNIVERSITY · PI SLY, WILLIAM S · 1988 to 2008
$4.3MComputational Resources for the Compilation and Distribution of Transcription FacR01GM084875 · NIGMS · UNIVERSITY OF BRITISH COLUMBIA · PI WASSERMAN, WYETH W · 2010 to 2012
$1.0MNIDDK NIH HHS DK40163NIDDK NIH HHS R01 DK040163NIGMS NIH HHS R01 GM084875NIGMS NIH HHS R01GM084875
Abstract
Four children in three unrelated families (one consanguineous) presented with lethargy, hyperlactatemia, and hyperammonemia of unexplained origin during the neonatal period and early childhood. We identified and validated three different CA5A alterations, including a homozygous missense mutation (c.697T>C) in two siblings, a homozygous splice site mutation (c.555G>A) leading to skipping of exon 4, and a homozygous 4 kb deletion of exon 6. The deleterious nature of the homozygous mutation c.697T>C (p.Ser233Pro) was demonstrated by reduced enzymatic activity and increased temperature sensitivity. Carbonic anhydrase VA (CA-VA) was absent in liver in the child with the homozygous exon 6 deletion. The metabolite profiles in the affected individuals fit CA-VA deficiency, showing evidence of impaired provision of bicarbonate to the four enzymes that participate in key pathways in intermediary metabolism: carbamoylphosphate synthetase 1 (urea cycle), pyruvate carboxylase (anaplerosis, gluconeogenesis), propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase (branched chain amino acids catabolism). In the three children who were administered carglumic acid, hyperammonemia resolved. CA-VA deficiency should therefore be added to urea cycle defects, organic acidurias, and pyruvate carboxylase deficiency as a treatable condition in the differential diagnosis of hyperammonemia in the neonate and young child.
Indexed as
AdolescentBase SequenceCarbonic Anhydrase VChildChild, PreschoolExonsFemaleGene DeletionGenetic VariationHomozygoteHumansHyperammonemiaInfantLiverMaleMolecular Sequence DataCarbonic Anhydrase V
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