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An infant with developmental regression and hypotonia has elevated lactate. MRI shows symmetric basal ganglia and brainstem lesions.
Heterogeneous (mtDNA or nuclear)
- SURF1, MT-ATP6, many others
- Subacute necrotizing encephalomyelopathy
- Developmental regression
- Hypotonia, dystonia, ataxia
- Respiratory abnormalities
- MRI: Symmetric lesions in basal ganglia, brainstem
- Elevated lactate in blood and CSF; lactate peak on MR spectroscopy
- MRI: bilateral symmetric T2/FLAIR signal in basal ganglia and brainstem is the unifying feature
- Confirmation: molecular testing (broad nuclear + mtDNA gene panel or exome/genome); muscle biopsy with respiratory-chain enzymology when molecular testing is non-diagnostic
- Supportive: no curative therapy
- Treat acute metabolic decompensation; avoid catabolic stress (fasting, illness)
- Cofactor/vitamin cocktails (thiamine, riboflavin, coenzyme Q10) are tried, with biotin/thiamine-responsive forms the clearest benefit
- Avoid sodium valproate (mitochondrial toxicity)
SURF1 = "FouR": SURF1 is an assembly factor for Complex IV (four). "SU'RF' = 'FouR'" rearranged. SURF1 mutations cause Leigh syndrome with Complex IV (cytochrome c oxidase) deficiency.
Genetically heterogeneous: Leigh syndrome can be caused by mutations in over 100 different genes (both nuclear and mitochondrial), all converging on mitochondrial energy production. The MRI pattern of symmetric basal ganglia and brainstem lesions is the unifying feature.