Mitochondrial disease

A 3-year-old girl is referred for developmental regression, exercise intolerance, and failure to thrive. She began walking at 18 months but has lost this skill over the past four months and now has a broad-based ataxic gait. Her maternal aunt has diabetes and deafness, and a maternal uncle lost his vision in his twenties. On examination she is short, hypotonic, and has pigmentary retinopathy on fundoscopy. Blood lactate is elevated at 5.2 mmol/L. Brain MRI shows bilateral symmetric basal-ganglia signal change. The case walks the candidate through the energy-failure phenotype, the dual-genome logic and the maternal family history, the tiered investigation from lactate to dual-genome sequencing to selective muscle biochemistry, the supportive management pillars including the mito cocktail and the critical drug avoidance (valproate in POLG disease), and the genetic counselling for maternal inheritance including the threshold effect and reproductive options.