Abstract
ObjectivesTo describe the spectrum of movement disorders and cerebrospinal fluid (CSF) neurotransmitter profiles in paediatric patients with POLG disease.MethodsWe identified children with genetically confirmed POLG disease, in whom CSF neurotransmitter analysis had been undertaken. Clinical data were collected retrospectively. CSF neurotransmitter levels were compared to both standardised age-related reference ranges and to non-POLG patients presenting with status epilepticus.ResultsForty-one patients with POLG disease were identified. Almost 50% of the patients had documented evidence of a movement disorder, including non-epileptic myoclonus, choreoathetosis and ataxia. CSF neurotransmitter analysis was undertaken in 15 cases and abnormalities were seen in the majority (87%) of cases tested. In many patients, distinctive patterns were evident, including raised neopterin, homovanillic acid and 5-hydroxyindoleacetic acid levels.ConclusionsChildren with POLG mutations can manifest with a wide spectrum of abnormal movements, which are often prominent features of the clinical syndrome. Underlying pathophysiology is probably multifactorial, and aberrant monoamine metabolism is likely to play a role.
Highlights
Mitochondrial DNA depletion syndromes (MDDS) are caused by defects in mtDNA maintenance due to mutations in nuclear genes which affect either mitochondrial deoxyribonucleoside triphosphate supply or components of the mtDNA replication machinery (Rahman and Poulton 2009)
We aimed to describe the clinical spectrum of movement disorders and cerebrospinal fluid (CSF) neurotransmitter profiles in children with POLG mutations
Paediatric patients (16 years or younger) with confirmed biallelic POLG mutations were retrospectively identified from the Oxford Rare Mitochondrial Disease Service for Adults and Children database, established in 2006
Summary
Mitochondrial DNA (mtDNA) depletion syndromes (MDDS) are caused by defects in mtDNA maintenance due to mutations in nuclear genes which affect either mitochondrial deoxyribonucleoside triphosphate supply or components of the mtDNA replication machinery (Rahman and Poulton 2009). DNA polymerase γ (pol γ) is essential for mtDNA replication and repair. Loss-offunction mutations of POLG, encoding the catalytic.
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