ArticleJournal of molecular medicine (Berlin, Germany)2020
Expanding and validating the biomarkers for mitochondrial diseases.
Article in Journal of molecular medicine (Berlin, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Mitochondrial DNA (mtDNA) as fluid biomarker in neurodegenerative disorders: A systematic review.European journal of neurology · 2025Pooled it
- A systematic review of the neuroprotective role and biomarker potential of GDF15 in neurodegeneration.Frontiers in immunology · 2024Pooled it
- Unraveling the role of FGF21 in epilepsy disease: mechanistic insights and therapeutic Potential.Metabolic brain disease · 2026Review
- Advances in diagnosis of mitochondrial dysfunction and primary mitochondrial disease.Disease models & mechanisms · 2026Review
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- Early hemodialysis in pediatric metformin overdose with severe lactic acidosis and recurrent hypoglycemia: a case report and literature review.Annals of medicine and surgery (2012) · 2026Article
- Non-invasive biomarkers for diagnosis and monitoring of primary mitochondrial diseases.Journal of neurology · 2026Review
- Untargeted Plasma Metabolomics Extends the Biomarker Profile of Mitochondrial Neurogastrointestinal Encephalomyopathy.International journal of molecular sciences · 2025Article
- The mitochondrial disease biomarker GDF15 is dynamic, quantifiable in saliva, and correlates with disease severity.Molecular genetics and metabolism · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Elevated circulating cell-free mitochondrial DNA level in cerebrospinal fluid of narcolepsy type 1.Brain communications · 2025Article
- The clinical utility in hospital-wide use of growth differentiation factor 15 as a biomarker for mitochondrial DNA-related disorders.Journal of inherited metabolic disease · 2025Article
- Review
- Somatic nuclear mitochondrial DNA insertions are prevalent in the human brain and accumulate over time in fibroblasts.PLoS biology · 2024Article
- Heightened Serum Mitochondrial Biomarkers; FGF21 and NOS in Pediatric Anemia and a Negative Correlation between GDF15 and Serum Ferritin.Journal of clinical medicine · 2024Article
- Biomarkers of mitochondrial disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Challenges and opportunities to bridge translational to clinical research for personalized mitochondrial medicine.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- The genetic landscape of mitochondrial diseases in the next-generation sequencing era: a Portuguese cohort study.Frontiers in cell and developmental biology · 2024Article
- Functional genomics and small molecules in mitochondrial neurodevelopmental disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Neuropathological hallmarks in autopsied cases with mitochondrial diseases caused by the mitochondrial 3243A>G mutation.Brain pathology (Zurich, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial diseases are highly heterogeneous metabolic disorders caused by genetic alterations in the mitochondrial DNA (mtDNA) or in the nuclear genome. In this study, we investigated a panel of blood biomarkers in a cohort of 123 mitochondrial patients, with prominent neurological and muscular manifestations. These biomarkers included creatine, fibroblast growth factor 21 (FGF21) and growth/differentiation factor 15 (GDF-15), and the novel cell free circulating-mtDNA (ccf-mtDNA). All biomarkers were significantly increased in the patient group. After stratification by the specific phenotypes, ccf-mtDNA was significantly increased in the Mitochondrial Encephalomyopathy Lactic Acidosis Stroke-like episodes syndrome (MELAS) group, and FGF21 and GDF-15 were significantly elevated in patients with MELAS and Myoclonic Epilepsy Ragged Red Fibers syndrome. On the contrary, in our cohort, creatine was not associated to a specific clinical phenotype. Longitudinal assessment in four MELAS patients showed increased levels of ccf-mtDNA in relation to acute events (stroke-like episodes/status epilepticus) or progression of neurodegeneration. Our results confirm the association of FGF21 and GDF-15 with mitochondrial translation defects due to tRNA mutations. Most notably, the novel ccf-mtDNA was strongly associated with MELAS and may be used for monitoring the disease course or to evaluate the efficacy of therapies, especially in the acute phase. KEY MESSAGES: • FGF21/GDF15 efficiently identifies mitochondrial diseases due to mutations in tRNA genes. • The novel ccf-mtDNA is associated with MELAS and increases during acute events. • Creatine only discriminates severe mitochondrial patients. • FGF21, GDF-15, and ccf-mtDNA are possibly useful for monitoring therapy efficacy.
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Registered trials
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