Myopathy with MTCYB mutation mimicking Multiple Acyl-CoA Dehydrogenase Deficiency

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Mitochondrial DNA (mtDNA) mutations are associated with various inherited disorders.
• Cytochrome b (CYB) is a crucial component of the mitochondrial electron transport chain and plays a role in cellular respiration.
• Pure myopathic presentations of mtDNA disorders can be challenging to diagnose.

Observation:

• Two pediatric patients presented with exercise intolerance, a pure myopathic phenotype.
• Genetic analysis identified novel mutations in the mtDNA CYB gene: m.15579A>G (p.Tyr278Cys) and m.15045G>A (p.Arg100Gln).
• Initial diagnostic workup revealed elevated medium- and long-chain acylcarnitines, mimicking other metabolic disorders.

Findings:

• The identified CYB mutations directly implicate this gene in the pathogenesis of the observed myopathy.
• The acylcarnitine profile was misleading, delaying the diagnosis of the underlying mitochondrial disorder.
• Cytochrome b's role in fatty acid oxidation is suggested by the clinical presentation and metabolic findings.

Implications:

• This study expands the spectrum of clinical phenotypes associated with CYB mutations.
• It underscores the importance of considering mtDNA disorders even with atypical metabolic profiles.
• Understanding the physiopathology of these mutations is crucial for accurate diagnosis and potential therapeutic strategies.