Progressive Myopathy and Respiratory Failure in a 7-Year-Old Boy With m.3251A>G MT-TL1 Mutation

We report a pediatric case of severe isolated mitochondrial myopathy because of the rare m.3251A>G variant of the MT-TL1 gene. A 7-year-old boy presented to the hospital with acute-on-chronic weakness and respiratory insufficiency. Initial laboratory tests were notable for elevated lactate, aldolase, and lactate dehydrogenase. Despite a negative autoimmune panel, he was presumed to have myositis and treated with steroids and intravenous immunoglobulin. He continued to deteriorate, eventually requiring intubation and ventilation. Muscle biopsy revealed numerous ragged red fibers, abnormal intracellular lipid droplets with no lymphocytic inflammation, and increased succinate dehydrogenase reactivity, reflecting mitochondrial proliferation in many fibers. Steroids were discontinued, and he was started on a mitochondrial cocktail of cofactors with clinical improvement. Genetic testing identified the m.3251A>G variant, confirming primary mitochondrial disorder. This case expands the known phenotype of the m.3251A>G mutation. We also discuss clinical and histopathological differences between mitochondrial and inflammatory myopathies.