Clinical and genetic spectrum in a cohort of patients with suspected mitochondrial disease

Introduction : Mitochondrial diseases (MDs) are a heterogeneous group of genetic disorders affecting oxidative phosphorylation, characterized by diverse neuromuscular and multisystemic manifestations, whose clinical variability and genetic complexity necessitate a comprehensive, multidisciplinary diagnostic approach. Aim : This study aims to explore the phenotypic and genotypic spectrum of patients with suspected MD, focusing on mitochondrial genome variations to improve diagnostic accuracy and support genetic counseling. Materials and methods : We analyzed 240 patients with a Nijmegen mitochondrial disease score (NMDS) ≥3, with 90 individuals undergoing comprehensive clinical, biochemical, neuroimaging, and genetic assessments. Descriptive statistics were applied to summarize clinical and biochemical data, while inferential analyses, including chi-square tests and regression models, were employed to explore genotype-phenotype associations. Results : The study delineated a multifaceted clinical spectrum, with neuromuscular dysfunction as the predominant hallmark, evidenced by a high prevalence of developmental delay (88.9%), hypotonia (77.8%), and exercise intolerance (63.3%). Patients with mitochondrial involvement displayed a significantly greater burden of neurological (seizures: 71.9% vs. 43.1%, p =0.009) and cardiac abnormalities (37.5% vs. 15.5%, p =0.018), underscoring their diagnostic relevance. Genetic analysis identified gene variants associated with the patients’ phenotypes in 35.6% of cases, with Complex I being the most frequently affected, emphasizing its pivotal role in mitochondrial dysfunction and disease severity. Conclusion : Our findings highlight the genetic and clinical heterogeneity of MDs, emphasizing the importance of integrating molecular, biochemical, and neuroimaging data to enhance early diagnosis and facilitate personalized treatment strategies.