Movement disorders in mitochondrial diseases.

Area of Science:

• Neurology
• Genetics
• Mitochondrial Biology

Background:

• Mitochondrial diseases (MIDs) are a diverse group of disorders caused by mutations in mitochondrial or nuclear DNA.
• These conditions often manifest with multisystem involvement, particularly affecting the central and peripheral nervous systems.
• Movement disorders are a common, though not exclusive, feature of MIDs.

Purpose of the Study:

• To review the spectrum of movement disorders associated with various mitochondrial diseases.
• To highlight specific genetic mutations and syndromes linked to particular movement disorder phenotypes.
• To guide clinicians in suspecting and diagnosing MIDs based on clinical and imaging findings.

Main Methods:

• Literature review of mitochondrial diseases and associated movement disorders.
• Analysis of clinical presentations, genetic causes (mtDNA and nDNA mutations), and specific syndromes.
• Correlation of movement disorder types (ataxia, myoclonus, dystonia, parkinsonism) with underlying genetic defects.

Main Results:

• Cerebellar ataxia is linked to MERRF, Kearns-Sayre syndrome, SANDO, ARCA2, Friedreich's ataxia, SPG7, SCA28, and ARSACS.
• Myoclonus is characteristic of MERRF and also seen in MELAS, ARCA2, POLG1 mutations, and Leigh syndrome.
• Dystonia is prevalent in Leigh syndrome and LHON plus disease, and also observed in ARCA2, PKAN, MPAN, and POLG1 mutations.

Conclusions:

• Movement disorders are a significant clinical manifestation across a wide range of mitochondrial diseases.
• Specific neurological signs and MRI findings, such as striatal necrosis, should prompt investigation for MIDs.
• Targeted genetic testing or muscle biopsy with metabolic/genetic studies are crucial for accurate diagnosis.