Primary mitochondrial disorders are highly variable in clinical presentation, biochemistry, and molecular etiology. Mitochondrial disorders can be caused by genetic defects in the mitochondrial, in nuclear genome, or in the interplay between the two genomes. Biochemical screening tests may be inconclusive or misleading since patients, with confirmed mitochondrial disorders specially in pediatric age, may exhibit normal routine biochemistry, muscle histology, or enzymatic analysis of the mitochondrial respiratory chain. Diagnosis is often challenging even with combination of multiple criteria (clinical, biochemical, histological, and functional), as innumerous conditions cause secondary mitochondrial dysfunction. Nowadays, a definite diagnosis is only possible by genetic confirmation since no single score system is satisfactorily accurate, being sensitive but not specific.
Conclusion: Awareness between physicians is of major importance considering that clinical suspicion may not be obvious regarding the heterogenicity in presentation and biochemical features of mitochondrial disorders. In this review, we provide information on diagnosis approach to patients suspected for mitochondrial disorders as well as management on chronic and acute settings. Follow-up should provide comprehensive information on patient’s status, since intervention on these diseases is mostly supportive and prognosis is variable and sometimes unpredictable.
What is Known:
• Mitochondrial disorders are heterogenous and may present at any age, with any symptoms and any type of inheritance.
• Mitochondrial disorders may be due to pathogenic variants in mitochondrial DNA (mtDNA) or nuclear genes (nDNA).
What is New:
• Since no single score system is satisfactorily accurate, a definite diagnosis is only possible with genetic studies with gene panels proving to be a cost-effective approach.
• Clinical and biochemical features of patients without a confirmed diagnosis must be reviewed and other diagnosis must be considered. A wider genetic approach may be applied (WES or WGS).