Leigh syndrome is a neurodegenerative disease associated with primary or secondary mitochondrial dysfunction at the level of oxidative phosphorylation.
Sofou et al. published a retrospective study describing patients with Leigh syndrome (n=130; 77 with pathogenic mutations) from eight European centers specializing in mitochondrial diseases. They described the natural history of Leigh syndrome and identified novel predictors of disease severity and long-term outcome.
The median age at presentation was 7 months, with 80% of patients presenting below 2 years old. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Increased CSF lactate was significantly correlated to a more severe disease course, characterized by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival.
The most common clinical features at onset were abnormal motor findings in ~80% of cases (e.g. hypotonia, dystonia) and abnormal ocular findings in 25% of patients (e.g. nystagmus, strabismus, visual impairment, optic atrophy, ptosis, ophthalmoplegia).
Clinical features throughout the disease course: more than 50% had at least three affected organ systems (most commonly, motor, visual and gastrointestinal systems). Epileptic seizures were present in 40% of patients, respiratory dysfunction in 38% (e.g. hyperventilation and/or abnormal breathing pattern, apnoea, obstructive or restrictive respiratory disease, central hypoventilation), and cardiac dysfunction in 18% (e.g. hypertrophic cardiomyopathy > arrhythmia/conduction defects > dilated cardiomyopathy).
A multicenter study on Leigh syndrome: disease course and predictors of survival. Sofou K, De Coo IF, Isohanni P, Ostergaard E, Naess K, De Meirleir L, Tzoulis C, Uusimaa J, De Angst IB, Lönnqvist T, Pihko H, Mankinen K, Bindoff LA, Tulinius M, Darin N. Orphanet J Rare Dis. 2014 Apr 15;9:52. doi: 10.1186/1750-1172-9-52. PMID: 24731534
Posted by Yannis Trakadis, MD