Silvia Marchet
FGF-21 AND GDF-15 AS CIRCULATING BIOMARKERS FOR MITOCHONDRIAL DISEASES. VALIDATION IN ONE-THOUSAND PLASMA SAMPLES.
Autori
- SILVIA MARCHET (IRCCS NEUROLOGICAL INSTITUTE CARLO BESTA – MILAN (ITALY) – MEDICAL BIOLOGIST)
- ANNA ARDISSONE (IRCCS NEUROLOGICAL INSTITUTE CARLO BESTA – MILAN (ITALY) – MEDICAL DOCTOR)
- KRISZTINA EINVAG (IRCCS NEUROLOGICAL INSTITUTE CARLO BESTA – MILAN (ITALY) – DATA SCIENTIST)
- DANIELE SALA (IRCCS NEUROLOGICAL INSTITUTE CARLO BESTA – MILAN (ITALY) – MEDICAL BIOTECNOLOGIST)
- ALESSIA CATANIA (IRCCS NEUROLOGICAL INSTITUTE CARLO BESTA – MILAN (ITALY) – MEDICAL DOCTOR)
- COSTANZA LAMPERTI (NEUROLOGICAL INSTITUTE CARLO BESTA – MILAN (ITALY) – MEDICAL DOCTOR)
Presentatore
SILVIA MARCHET – IRCCS NEUROLOGICAL INSTITUTE CARLO BESTA – MILAN (ITALY)
Modalità
Poster Session
Abstract
Mitochondrial Diseases (MDs) are rare multisystem disorders caused by genetic alterations in the mitochondrial DNA (mtDNA) or in the nuclear DNA (nDNA).
To date, available biomarkers are still not completely suitable for diagnosis, patients’ stratification, evaluation of disease severity, progression and response to treatments.
In particular, the reliability of circulating FGF-21 and GDF-15 as biomarkers for MDs is still unclear due to the small cohorts of patients in which these two cytokines were recently studied and to the extreme variability of the MDs phenotypes.
To overcome these biases and validate FGF-21 and GDF-15 as biomarkers for MDs, one-thousand peripheral blood samples were collected from 515 MDs patients, both paediatrics and adults, recruited at the IRCCS Istituto Neurologico C. Besta (Milan) and from age-matched heathy controls.
All patients underwent demographic, genetic, functional and clinical assessments, including clinical scales NMDPS/NMDAS (Newcastle Mitochondrial Disease Paediatrics/Adult Scales). Samples were collected at each visit during a period of 8 years and the FGF-21 and GDF-15 plasma levels were measured by ELISA method.
We found that in MDs manifesting with predominant muscle involvement, such as those associated to mt-tRNA mutations (MELAS, MERRF) and to mtDNA single or multiple deletions (KSS, PEO), both molecules were significantly increased compared to MDs without myopathic features (encephalopathy, ADOA, LHON, NARP, PKAN, ataxia…), mostly caused by nDNA mutations.
Our data confirmed that FGF-21 and GDF-15 can discriminate controls from MDs patients and patients carrying nDNA defects from those with mtDNA defects, correlating with specific clinical features and disease severity.