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POLG1 manifestations in childhood
P Isohanni1, A H Hakonen, L Euro
1University of Helsinki, Helsinki, Finland. pirjo.isohanni@helsinki.fi
Neurology
|March 2, 2011
Summary
Mitochondrial DNA polymerase gamma (POLG1) mutations can cause severe childhood encephalopathy with epilepsy, even with normal muscle tests. Early POLG1 genetic testing is crucial before valproate treatment in at-risk children.
Area of Science:
- Genetics
- Neurology
- Mitochondrial Diseases
Background:
- Mutations in mitochondrial DNA polymerase gamma (POLG1) are linked to Alpers syndrome in children and mitochondrial recessive ataxia syndrome (MIRAS) in adults.
- Some MIRAS patients exhibit childhood-onset ataxia or epilepsy, suggesting POLG1 mutations may present earlier than typically recognized.
Purpose of the Study:
- To investigate the prevalence and clinical spectrum of POLG1 mutations in children with unexplained neurological manifestations.
Main Methods:
- Genetic analysis of POLG1 in 136 children suspected of mitochondrial disease.
- Clinical evaluation included ataxia, neuropathy, severe epilepsy, epileptic encephalopathy, encephalohepatopathy, or Alpers syndrome.
Main Results:
- Seven patients (5.1%) had POLG1 mutations, all presenting with severe encephalopathy and intractable epilepsy.
- Four patients died after sodium valproate exposure; brain MRI revealed specific lesions and abnormalities.
- Muscle histology and mitochondrial biochemistry were normal in all affected patients.
Conclusions:
- POLG1 genetic testing should be a first-line diagnostic tool for children with encephalitis-like symptoms progressing to epileptic encephalopathy and liver involvement (Alpers syndrome).
- POLG1 analysis is recommended before initiating valproate therapy in pediatric patients with a compatible phenotype.
- POLG1 mutations are not a frequent cause of isolated childhood epilepsy or ataxia.
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