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Mitochondrial Clinical & Research Network (MCRN)

 

A multinational collaboration of experts on mitochondrial disease

 

Research project on Leigh syndrome: Published results

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Symptoms at onset of Leigh syndrome

 

Copyright © 2014 Sofou et al.; licensee BioMed Central Ltd.

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.

 

Background

Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients.

Methods

This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu.

Results

A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, with 80.8% of patients presenting by the age of 2 years. The most common clinical features were abnormal motor findings, followed by abnormal ocular findings. Epileptic seizures were reported in 40% of patients. Approximately 44% of patients experienced acute exacerbations requiring hospitalisation during the previous year, mainly due to infections. [Read more]

 

Orphanet J Rare Dis. 2014 Apr 15;9:52 [Full text]

 

Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients.

 

Sofou K, De Coo IF, Ostergaard E, Isohanni P, Naess K, De Meirleir L, Tzoulis C, Uusimaa J, Lönnqvist T, Bindoff LA, Tulinius M, Darin N.

 

BACKGROUND:

Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored.

OBJECTIVE:

We aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients.

METHODS:

We studied 96 patients with genetically confirmed Leigh syndrome diagnosed and followed in eight European centres specialising in mitochondrial diseases.

RESULTS:

We found that ataxia, ophthalmoplegia and cardiomyopathy were more prevalent among patients with mitochondrial DNA defects. Patients with mutations in MT-ND and NDUF genes with complex I deficiency shared common phenotypic features, such as early development of central nervous system disease, followed by high occurrence of cardiac and ocular manifestations. The cerebral cortex was affected in patients with NDUF mutations significantly more often than the rest of the cohort. [Read more]

 

J Med Genet. 2018 Jan;55(1):21-27.

 

 

 

 

Ongoing research projects on Leigh syndrome

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To develop MRI pattern recognition methods in Leigh syndrome