Clinical, biochemical, and genetic findings in a group of patients evaluated for suspected mitochondrial disorders

Mitochondrial diseases (MDs) are clinically heterogeneous disorders caused by mutations in either mitochondrial DNA (mtDNA) or nuclear genes that impair oxidative phosphorylation. This study aimed to comprehensively characterize the clinical, biochemical, imaging, and molecular features of 37 patients exhibiting mitochondrial involvement, selected from a larger group of 240 individuals with suspected MD based on a Nijmegen Mitochondrial Disease Score ≥3. All patients underwent a standardized evaluation protocol comprising clinical assessment, targeted biochemical and instrumental investigations, qPCR-HRM screening for common mtDNA mutations, and mtDNA sequencing, with additional nuclear gene analysis performed in selected cases. Multisystemic involvement was prevalent, with neuromuscular and central nervous system manifestations being the most frequent. Elevated lactate levels and abnormal neuroimaging findings further supported the clinical diagnosis. Molecular analyses revealed both common and rare mtDNA variants, while nuclear gene defects were identified in a subset of patients, underscoring the genetic complexity of MDs. The integrated approach enabled accurate diagnosis and highlighted the value of combining clinical and molecular data in MD evaluation.