Metabolic and mitochondrial alterations in children with autism spectrum disorder: The role of FGF-21 and GDF-15
Clinica Chimica Acta, cilt.588, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 588
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.cca.2026.120979
- Dergi Adı: Clinica Chimica Acta
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Anahtar Kelimeler: Amino acid, Autism spectrum disorder, Biomarkers, Fibroblast growth factor 21, Growth differentiation factor 15, Mitochondrial stress
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Introduction Autism Spectrum Disorder (ASD) is a neurodevelopmental condition marked by social communication deficits and repetitive behaviors. Evidence suggests that metabolic and mitochondrial stress contribute to ASD. Fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) are circulating markers of mitochondrial dysfunction and cellular stress, but their role in pediatric ASD remains underexplored. Methods Case–control study involved 118 children: 88 with ASD (DSM-5 criteria) and 30 healthy controls matched by age and sex. ASD patients were divided by Autism Behavior Checklist (ABC) scores into Group I (ABC >60, n = 48) and Group II (ABC ≤60, n = 40). FGF-21 and GDF-15 were measured by ELISA. Biochemical parameters, hemogram, plasma amino acids (LC-MS/MS), and urinary organic acids (GC–MS) were analyzed. Statistical analyses included Kruskal–Wallis, Spearman correlation and ROC. Results FGF-21 was significantly elevated in ASD compared to controls (p < 0.0001), while GDF-15 showed no difference (p = 0.797). FGF-21 did not differ between Group I and Group II (p > 0.05). ASD showed increased lactate, lactate/pyruvate ratio, urea, AST, LDH, LDL, lymphocyte and platelet counts, and decreased pyruvate, serum and urinary creatinine (p < 0.05). Essential and branched-chain amino acids decreased, whereas glycine and histidine increased (p < 0.05). FGF-21 correlated weakly but significantly with mitochondrial dysfunction and amino acid metabolism markers. ROC showed good diagnostic accuracy for FGF-21 in ASD (AUC = 0.817), with 98.9% sensitivity and 73.3% specificity at 27.9 pg/mL cut-off. Urinary organic acids, methylmalonic acid, tiglylglycine, and 2-ketoisocaproic acid, were significantly elevated (p < 0.05). Conclusion Elevated serum FGF-21 in children with ASD is linked to metabolic alterations, whereas GDF-15 remains unchanged. These results suggest FGF-21's association with metabolic dysregulation in ASD.