Expanding and validating the biomarkers for mitochondrial diseases.
J Mol Med (Berl)
; 98(10): 1467-1478, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32851462
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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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Biomarcadores
/
Enfermedades Mitocondriales
/
Susceptibilidad a Enfermedades
/
Mitocondrias
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
J Mol Med (Berl)
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2020
Tipo del documento:
Article