A patient with two mitochondrial DNA mutations causing PEO and LHON

Area of Science:

• Genetics
• Neurology
• Mitochondrial Diseases

Background:

• Mitochondrial DNA (mtDNA) mutations are linked to various neuromuscular and neurodegenerative disorders.
• Progressive external ophthalmoplegia (PEO) and Leber hereditary optic neuropathy (LHON) are distinct conditions associated with mtDNA defects.

Observation:

• A 22-year-old male presented with PEO preceding optic atrophy.
• Muscle biopsy revealed mitochondrial myopathy with cytochrome c oxidase deficient fibers.
• Skeletal muscle showed homoplasmic G11778A LHON mutation and heteroplasmic 5 kb deletion.

Findings:

• The patient was homoplasmic for the G11778A LHON mutation and heteroplasmic for a 5 kb mtDNA deletion in muscle tissue.
• Blood analysis identified only the homoplasmic LHON mutation.
• The co-occurrence of two pathogenic mtDNA mutations was observed.

Implications:

• This case demonstrates a rare instance of combined pathogenic mtDNA mutations.
• The findings suggest the mtDNA deletion mutation caused PEO, while the LHON mutation caused optic atrophy.
• Understanding dual mtDNA mutations is crucial for diagnosing complex phenotypes.