ReviewJournal of inherited metabolic disease2011
Cobalamin C defect: natural history, pathophysiology, and treatment.
Review in Journal of inherited metabolic disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01793090 (Phase 2, Double-Blind, Placebo Controlled Clinical Trial of EPI-743 in Subjects With Cobalamin C Defect), which is not on this map. Cited by 78 papers, 2 of them syntheses 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.
Phase 2, Double-Blind, Placebo Controlled Clinical Trial of EPI-743 in Subjects With Cobalamin C Defect
Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 149 citations in OpenAlex.
- Genetics of catatonia: a systematic review of case reports and a gene pathway analysis.European psychiatry : the journal of the Association of European Psychiatrists · 2025Pooled it
- Newborn screening for homocystinurias and methylation disorders: systematic review and proposed guidelines.Journal of inherited metabolic disease · 2015Pooled it
- Advanced Ophthalmic Drug Delivery in Homocystinuria Type CblC: A Translational Review of Ophthalmic Pathologies and Therapeutic Opportunities.Pharmaceutics · 2026Review
- Cobalamin-Related Remethylation Disorders: Pregnancy Outcomes and Prenatal Treatment-New Cases and a Literature Study.Journal of inherited metabolic disease · 2026Review
- The relationship between cobalamin C deficiency and unexplained pediatric pulmonary hypertension.Pediatric research · 2026Article
- Clinical Outcomes and Correlation With Biochemical Control in Hydroxocobalamin-Treated Patients With Early-Onset Cobalamin C Disease.JIMD reports · 2026Article
- Review
- Branched Chain Amino Acid Metabolism in Developmental Brain Injury: Putative Mechanisms and Therapeutic Potential.Developmental neuroscience · 2026Review
- Timely Diagnosis of Cobalamin C Disease via Rapid Genome Sequencing in a Neonate With Severe Prenatally Detected Biventricular Dysfunction.Case reports in critical care · 2026Article
- Recent research advances in the biological function and molecular mechanism of methylmalonic acid.Journal of Zhejiang University. Science. B · 2025Review
- Milder Form of Cobalamin C Disease May Be Missed by Newborn Screening: The Importance of Methylmalonic Acid Assessment.International journal of neonatal screening · 2025Article
- A Comprehensive Overview of Subacute Combined Degeneration: MRI Diagnostic Challenges and Treatment Pathways.Brain sciences · 2025Review
- Faster, affordable, and reliable diagnosis of cobalamin C disease by targeted sequencing.Pediatric research · 2025Article
- Cobalamin C deficiency: a rare but treatable genetic cause of pulmonary hypertension.Orphanet journal of rare diseases · 2025Article
- Long-term outcome of CblC deficiency complicated with pulmonary hypertension.Orphanet journal of rare diseases · 2025Article
- Diagnostic Value of Biological Parameters in Biopsy-Confirmed Thrombotic Microangiopathy-MATRIX Consortium Group.Kidney international reports · 2025Article
- Multifaceted Clinical Spectrum of Vitamin B12 Deficiency - a Case Report and Literature Review.Journal of blood medicine · 2025Article
- Case Report: Dilated cardiomyopathy as the initial presentation in an adult with late-onset CblC defect.Frontiers in cardiovascular medicine · 2025Article
- Improved biochemical and neurodevelopmental profiles with high-dose hydroxocobalamin therapy in cobalamin C defect.Journal of inherited metabolic disease · 2025Article
- Late-onset renal TMA and tubular injury in cobalamin C disease: a report of three cases and literature review.BMC nephrology · 2024Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cobalamin C (Cbl-C) defect is the most common inborn cobalamin metabolism error; it causes impaired conversion of dietary vitamin B12 into its two metabolically active forms, methylcobalamin and adenosylcobalamin. Cbl-C defect causes the accumulation of methylmalonic acid and homocysteine and decreased methionine synthesis. The gene responsible for the Cbl-C defect has been recently identified, and more than 40 mutations have been reported. MMACHC gene is located on chromosome 1p and catalyzes the reductive decyanation of CNCbl. Cbl-C patients present with a heterogeneous clinical picture and, based on their age at onset, can be categorized into two distinct clinical forms. Early-onset patients, presenting symptoms within the first year, show a multisystem disease with severe neurological, ocular, haematological, renal, gastrointestinal, cardiac, and pulmonary manifestations. Late-onset patients present a milder clinical phenotype with acute or slowly progressive neurological symptoms and behavioral disturbances. To improve clinical course and metabolic abnormalities, treatment of Cbl-C defect usually consists of a combined approach that utilizes vitamin B12 to increase intracellular cobalamin and to maximize deficient enzyme activities, betaine to provide a substrate for the conversion of homocysteine into methionine through betaine-homocysteine methyltransferase, and folic acid to enhance remethylation pathway. No proven efficacy has been demonstrated for carnitine and dietary protein restriction. Despite these measures, the long-term follow-up is unsatisfactory especially in patients with early onset, with frequent progression of neurological and ocular impairment. The unfavorable outcome suggests that better understanding of the pathophysiology of the disease is needed to improve treatment protocols and to develop new therapeutic approaches.
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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.