| Normal | 5-33 repeats |
| Intermediate (carrier) | 34-66 repeats |
| Pathological | 66-1700 repeats[@monros1999] |
| Reduced Fe-S cluster synthesis | Impaired assembly of Fe-S clusters affects the function of multiple enzymes including aconitase, complexes I-III, and electron transfer flavoprotein[@muhlenhoff2018] |
| Iron accumulation | Mitochondrial iron overload with normal cytosolic iron levels leads to oxidative damage through Fenton chemistry[@bradley2000] |
| Energy failure | Reduced ATP production due to impaired oxidative phosphorylation[@rtig1997a] |
| Increased reactive oxygen species (ROS) | Elevated ROS production causing lipid peroxidation, protein oxidation, and DNA damage[@emond2000] |
| Dorsal root ganglia (DRG) | Most severely affected, with neurons loss, demyelination, and gliosis[@koeppen2009] |
| Cardiac muscle | Hypertrophic cardiomyopathy with fibrosis, leading to heart failure[@weidemann2019] |
| Cerebellar Purkinje cells | Progressive degeneration leading to ataxia[@koeppen2012] |
| Pancreatic β-cells | Impaired insulin secretion leading to diabetes mellitus[@cnop2008] |
| Skeletal muscle | Variable involvement with reduced exercise tolerance[@lodi2002] |
| Databases | OMIMOrphanetClinicalTrialsPubMed |