A multicenter study on Leigh syndrome: disease course and predictors of survival

Orphanet Journal of Rare Diseases

Niklas Darin⁹  Már Tulinius⁹  Laurence A Bindoff⁷  Katariina Mankinen¹  Helena Pihko⁶  Tuula Lönnqvist⁶  Isabell B De Angst⁴  Johanna Uusimaa⁵  Charalampos Tzoulis⁷  Linda De Meirleir^1,10  Karin Naess²  Elsebet Ostergaard⁸  Pirjo Isohanni³  Irenaeus F M De Coo⁴  Kalliopi Sofou⁹ 

[1] Länsi-Pohja Central Hospital, Kemi, Finland;Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden;Research Programs Unit, Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland;Department of Neurology, Erasmus MC, Rotterdam, The Netherlands;Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland;Department of Paediatric Neurology, Children’s Hospital, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland;Department of Clinical Medicine, University of Bergen, Bergen, Norway;Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark;Department of Paediatrics, University of Gothenburg, The Queen Silvia’s Children Hospital, SE-416 85 Gothenburg, Sweden;Department of Paediatric Neurology, University Hospital Vrije Universiteit Brussel (VUB), Brussels, Belgium

关键词: Diagnostic criteria;    Prognosis;    Relapse;    Survival;    Natural history;    Leigh syndrome;   

Others  :  863207
DOI  :  10.1186/1750-1172-9-52

 received in 2013-11-30, accepted in 2014-04-07,  发布年份 2014

【 摘 要 】

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. The presence of pathological signs at birth and a history of epileptic seizures were associated with higher occurrence of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal fluid was significantly correlated to a more severe disease course, characterised by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival.

Conclusions

This is a multicenter study performed in a large cohort of patients with Leigh syndrome. Our data help define the natural history of Leigh syndrome and identify novel predictors of disease severity and long-term prognosis.

【 授权许可】

   
2014 Sofou et al.; licensee BioMed Central Ltd.

【 图 表 】

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