ArticleGenetics in medicine : official journal of the American College of Medical Genetics2016
Defective hepatic bicarbonate production due to carbonic anhydrase VA deficiency leads to early-onset life-threatening metabolic crisis.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature.Orphanet journal of rare diseases · 2020Pooled it
- Clinical and biochemical footprints of inherited metabolic disorders: XIX. Hypoglycemia.Molecular genetics and metabolism · 2026Review
- Long-Term Follow-Up of Patients With Mitochondrial Carbonic Anhydrase VA Deficiency. A Case Report and Literature Review.JIMD reports · 2026Article
- Article
- A novel homozygous CA5A gene deletion in carbonic anhydrase VA deficiency presenting as developmental delay without metabolic crisis.Molecular genetics and metabolism reports · 2026Article
- Antenatal and Neonatal Management of Siblings With Carbonic Anhydrase VA Deficiency.JIMD reports · 2026Article
- Carbonic anhydrase VA deficiency due to a novelMolecular genetics and metabolism reports · 2025Article
- Review
- 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
- Carbonic anhydrase 8 regulates basophil activation and interleukin 4 production.Frontiers in immunology · 2025Article
- Quo vadis ureagenesis disorders? A journey from 90 years ago into the future.Journal of inherited metabolic disease · 2024Review
- A founder mutation inJIMD reports · 2024Article
- Theoretical Improvements in Enzyme Efficiency Associated with Noisy Rate Constants and Increased Dissipation.Entropy (Basel, Switzerland) · 2024Article
- FDA-approved carbonic anhydrase inhibitors reduce amyloid β pathology and improve cognition, by ameliorating cerebrovascular health and glial fitness.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Mitochondrial carbonic anhydrase VA and VB: properties and roles in health and disease.The Journal of physiology · 2023Review
- Hyperammonemia in Russia Due to Carbonic Anhydrase VA Deficiency Caused by Homozygous Mutation p.Lys185Lys (c.555G>A) of the CA5A GeneInternational journal of molecular sciences · 2022Article
- Article
- A case of carbonic anhydrase type VA deficiency presenting as West syndrome in an infant with a novel mutation in the CA-VA gene.Epilepsy & behavior reports · 2022Article
- Tip60 might be a candidate for the acetylation of hepatic carbonic anhydrase I and III in mice.Molecular biology reports · 2021Article
- Structural and Functional Characterization of Covalently Modified Proteins Formed By a Glycating Agent, Glyoxal.ACS omega · 2021Article
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
12 authors at 9 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeFour mitochondrial metabolic liver enzymes require bicarbonate, which is provided by the carbonic anhydrase isoforms VA (CAVA) and VB (CAVB). Defective hepatic bicarbonate production leads to a unique combination of biochemical findings: hyperammonemia, elevated lactate and ketone bodies, metabolic acidosis, hypoglycemia, and excretion of carboxylase substrates. This study aimed to test for CAVA or CAVB deficiencies in a group of 96 patients with early-onset hyperammonemia and to prove the disease-causing role of the CAVA variants found.
methodsWe performed CA5A and CA5B sequencing in the described cohort and developed an expression system using insect cells, which enabled the characterization of wild-type CAVA, clinical mutations, and three variants that affect functional residues.
resultsIn 10 of 96 patients, mutations in CA5A were identified on both alleles but none in CA5B. Exhibiting decreased enzyme activity or thermal stability, all CAVA mutations were proven to cause disease, whereas the three variants showed no relevant effect.
conclusionCAVA deficiency is a differential diagnosis of early-onset and life-threatening metabolic crisis, with hyperammonemia, hyperlactatemia, and ketonuria as apparently obligate signs. It seems to be more common than other rare metabolic diseases, and early identification may allow specific treatment of hyperammonemia and ultimately prevent neurologic sequelae.Genet Med 18 10, 991-1000.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.