Mitokondriyal Hastalık Tanılı Hastaların Semptom ve Bulgularının Mitokondriyal Hastalık Tanı Kriterleri ile Değerlendirilmesi

Abstract

Yıldız S. Evaluation of Symptoms and Findings of Patients Diagnosed with Mitochondrial Disease According to Mitochondrial Disease Diagnostic Criteria. Hacettepe University Faculty of Medicine, Department of Pediatrics, Ankara, 2026. Mitochondrial diseases constitute a genetically and phenotypically heterogeneous group of disorders resulting from mutations in mitochondrial DNA or nuclear DNA encoding structural and functional mitochondrial proteins. As mitochondria are present in nearly all cells except mature erythrocytes and play a central role in cellular energy metabolism, mitochondrial dysfunction may affect multiple organs and systems throughout the body. Tissues with high energy demand, particularly the brain, skeletal muscle, heart, and eyes, are most frequently involved. Clinical manifestations vary widely and may include developmental delay, developmental regression, seizures, encephalopathy, hypotonia, and visual or hearing impairment, making the diagnosis of mitochondrial diseases particularly challenging. The aim of this study was to evaluate the clinical, laboratory, imaging, histopathological, and genetic findings of patients followed with a diagnosis of mitochondrial disease at Hacettepe University İhsan Doğramacı Children’s Hospital. Patients were assessed for multisystem involvement according to established diagnostic criteria for mitochondrial diseases and were classified as unlikely, possible, probable, or definite cases. Among the 144 patients included in the study, three were classified as unlikely, twenty-eight as possible, fifty-seven as probable, and fifty-six as definite mitochondrial disease cases. When compared with the remaining patient groups, the definite case group showed significantly higher rates of mortality, multisystem involvement, muscle weakness, history of seizures and migraine, dysphagia, failure to thrive, hepatomegaly, optic neuropathy, and optic atrophy. In addition, statistically significant differences were observed between groups with respect to elevated serum lactate, creatine kinase, alanine, lactate/pyruvate ratio, and alanine aminotransferase levels; increased urinary excretion of lactate, pyruvate, and dicarboxylic acids on organic acid analysis; abnormal cranial magnetic resonance imaging findings including basal ganglia signal changes, stroke-like lesions, and cerebral atrophy; as well as the presence of a lactate peak on cranial magnetic resonance spectroscopy. Genetic confirmation was achieved in 33 of the 56 patients classified as definite cases. Evaluation of this genetically confirmed subgroup revealed genotype–phenotype correlations consistent with previously reported cases in the literature. Due to their heterogeneous clinical presentation and potential to affect multiple organ systems simultaneously, mitochondrial diseases require a multisystemic and multidisciplinary diagnostic approach. The rational integration of rapidly evolving next-generation genetic diagnostic methods with established clinical diagnostic criteria has the potential to significantly shorten the diagnostic process. Prioritizing this comprehensive approach in clinical practice may contribute substantially to early diagnosis, appropriate follow-up, and effective genetic counseling.