Leigh Syndrome, a mitochondrial disease with a prevalence of 1-in-40000, displays genetic diversity, with 15% exhibiting complex 4 deficiency, notably due to pathogenic SURF1 variants.(1,2) This study explores two cases with a SURF1 variant, one with a novel mutation. Both patients had developmental delay upon diagnosis, but had not experienced attacks leading to metabolic decompensation; maintaining stable neurologic and social functions. Despite mitochondrial therapy, sudden respiratory failure and metabolic decline resulted in dependency on respiratory support, encephalopathy and severe neuromotor retardation. The first case, aged 23 months, was brought in due to inability to walk independently. The second case, at 18 months, was referred for acidosis; he had a coarse face with hirsutism features.Treatment involved a low glycemic index diet enriched with supplements fort he first case and coenzyme-Q10 supplementation for the second. Both cases remained neurologically stable initially but faced acute respiratory distress and metabolic decompensation during treatment, leading to extended intensive care, tracheostomy, and home-ventilator support. In SURF-1-related Leigh Syndrome, common mutations are c.845_846delCT and c.312_312del10insAT, while in Turkey, c.796G>A has been reported frequently.(3,4) Our first case had a previously unreported frameshift mutation, c.498_493del, and the second case had a pathogenic c. .845_846del mutation. Leigh Syndrome is mostly diagnosed during acute respiratory failure and metabolic decompensation. While there is no cure, vitamin and cofactor supplementation aims to prevent future attacks.(5) Despite early intervention, both cases experienced disease progression and severe permanent sequelae. Early diagnosis before the vegetative state, offers hope, emphasizing the importance of specific treatment development.

Burcu Karakayalı
Marmara University School of Medicine
Turkey

Emine Genc
Marmara University School of Medicine
Turkey

Hamza Polat
Marmara University School of Medicine
Turkey

Eda Almus
Marmara University School of Medicine
Turkey

Burcu Öztürk Hışmi
Marmara University School of Medicine
Turkey

Olcay Ünver
Marmara University School of Medicine
Turkey

Dilşad Türkdoğan
Marmara University School of Medicine
Turkey