When to Suspect and How to Diagnose Mitochondrial Disorders?

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Mitochondrial respiratory chain disorders are diverse, affecting any tissue, age, or inheritance pattern.
• Diagnosis necessitates understanding clinical phenotypes and utilizing various laboratory techniques.
• Limited availability of respiratory chain studies in India poses diagnostic challenges.

Purpose of the Study:

• To outline diagnostic strategies for mitochondrial respiratory chain disorders.
• To emphasize the importance of appropriate laboratory testing.
• To caution against premature exome sequencing without preceding mitochondrial studies.

Main Methods:

• Review of diagnostic approaches for mitochondrial disorders.
• Highlighting the role of biochemical and histochemical studies on muscle biopsy.
• Discussing the selection of molecular genetic studies based on initial findings.

Main Results:

• A stepwise diagnostic approach is recommended, often starting with muscle biopsy.
• Specific genetic tests are suitable for certain syndromes.
• Exome sequencing without prior mitochondrial evaluation can be misleading.

Conclusions:

• Accurate diagnosis of mitochondrial disorders relies on a combination of clinical evaluation and appropriate laboratory testing.
• Muscle biopsy remains a crucial tool for initial assessment.
• Prioritizing mitochondrial studies before broad genetic testing is essential to avoid diagnostic errors.