Adult‐Onset Leigh Syndrome due to SURF1 Mutations

Leigh syndrome (LS) or subacute necrotising encephalomyelopathy is a heterogeneous disorder. LS can be sporadic or familial. It is typically seen in infancy or childhood, although cases of adult onset have been reported. Over 100 different monogenic disorders associated with large clinical and biochemical heterogeneity have been described. Herein, we report a mild very late adult‐onset LS revealed in a 36‐year‐old man who presented with diplopia and walking difficulties. Cerebral MRI showed midbrain abnormalities sparing substantia nigra and red nuclei along with pons abnormalities demonstrating the “double panda sign”. Muscle biopsy confirmed mitochondrial dysfunction showing a proliferation of mitochondria, and the presence of COX‐negative muscle fibres and ragged red fibres, while respiratory chain enzyme activity was decreased in cultured skeletal muscle and skin fibroblast. DNA analysis disclosed a homozygous SURF1 gene mutation in Exon 1, predicted to provoke a frameshift and premature stop codon. The importance of MRI as a diagnostic aid is highlighted, followed by DNA‐based diagnosis. In the absence of clear genotype–phenotype correlation in SURF1 ‐related LS, the collection of all LS‐associated mutations appears important while gene replacement therapies are being investigated for SURF1 ‐related LS.