ArticleOrphanet journal of rare diseases2014
Follow-up of folinic acid supplementation for patients with cerebral folate deficiency and Kearns-Sayre syndrome.
Article in Orphanet journal of rare diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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
16 citing papers in PubMed, 46 citations in OpenAlex.
- Current global vitamin and cofactor prescribing practices for primary mitochondrial diseases: Results of a European reference network survey.Journal of inherited metabolic disease · 2025Article
- Mitochondrial Chronic Progressive External Ophthalmoplegia.Brain sciences · 2024Review
- Metabolomic disorders: confirmed presence of potentially treatable abnormalities in patients with treatment refractory depression and suicidal behavior.Psychological medicine · 2023Article
- Cerebral folate deficiency: A report of two affected siblings.Molecular genetics and metabolism reports · 2023Article
- Folic acid inhibits 5-methyltetrahydrofolate transport across the blood-cerebrospinal fluid barrier: Clinical biochemical data from two cases.JIMD reports · 2022Article
- Cerebral Folate Deficiency Syndrome: Early Diagnosis, Intervention and Treatment Strategies.Nutrients · 2022Review
- Endocrine Manifestations and New Developments in Mitochondrial Disease.Endocrine reviews · 2022Article
- Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis.Journal of personalized medicine · 2021Review
- Current and Emerging Clinical Treatment in Mitochondrial Disease.Molecular diagnosis & therapy · 2021Review
- Mitochondrial medicine therapies: rationale, evidence, and dosing guidelines.Current opinion in pediatrics · 2020Review
- The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions.Brain sciences · 2020Article
- Emerging Concepts in Nutrient Needs.The Journal of nutrition · 2020Review
- Targeted versus untargeted omics - the CAFSA story.Journal of inherited metabolic disease · 2018Article
- Folate nutrition and blood-brain barrier dysfunction.Current opinion in biotechnology · 2017Review
- Dietary Supplement for Core Symptoms of Autism Spectrum Disorder: Where Are We Now and Where Should We Go?Frontiers in psychiatry · 2017Review
- Neurometabolic Disorders: Potentially Treatable Abnormalities in Patients With Treatment-Refractory Depression and Suicidal Behavior.The American journal of psychiatry · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundKearns-Sayre syndrome (KSS) is a mitochondrial DNA deletion syndrome that presents with profound cerebral folate deficiency and other features. Preliminary data support the notion that folinic acid therapy might be useful in the treatment of KSS patients. Our aim was to assess the clinical and neuroimaging outcomes of KSS patients receiving folinic acid therapy.
methodsPATIENTS: We recruited eight patients with diagnoses of KSS. Four cases were treated at 12 de Octubre Hospital, and the other two cases were treated at Sant Joan de Déu Hospital. Two patients refused to participate in the treatment protocol.
methodsClinical, biochemical and neuroimaging data (magnetic resonance imaging or computed tomography scan) were collected in baseline conditions and at different time points after the initiation of therapy. Cerebrospinal fluid 5-methyltetrahydrofolate levels were analysed with HPLC and fluorescence detection. Large-scale mitochondrial DNA deletions were analysed by Southern blot. TREATMENT PROTOCOL: The follow-up periods ranged from one to eight years. Cases 1-4 received oral folinic acid at a dose of 1 mg/kg/day, and cases 6 and 8 received 3 mg/kg/day.
resultsNo adverse effects of folinic acid treatment were observed. Cerebral 5-methyltetrahydrofolate deficiencies were observed in all cases in the baseline conditions. Moreover, all three patients who accepted lumbar puncture after folinic acid therapy exhibited complete recoveries of their decreased basal cerebrospinal fluid 5-methyltetrahydrofolate levels to normal values. Two cases neurologically improved after folinic therapy. Disease worsened in the other patients. Post-treatment neuroimaging was performed for the 6 cases that received folinic acid therapy. One patient exhibited improvements in white matter abnormalities. The remaining patients displayed progressions in subcortical cerebral white matter, the cerebellum and cerebral atrophy.
conclusionsFour patients exhibited clinical and radiological progression of the disease following folinic acid treatment. Only one patient who was treated in an early stage of the disease exhibited both neurological and radiological improvements following elevated doses of folinic acid, and an additional patient experienced neurological improvement. Early treatment with high-dose folinic acid therapy seems to be advisable for the treatment of KSS.
trial registrationEudrac T2007-00-6748-23.
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.