Professor Jo Poulton, Professor Shamima Rahman and Dr Mike Champion were among several experts in mitochondrial medicine who co-authored the article in the Journal of Inherited Metabolic Disease. It is the latest example of Lily Foundation associates working to improve the understanding of mitochondrial disease through high-quality research.
The study used the Oxford Rare Mitochondrial Disease Service for Adults and Children database to identify 41 paediatric patients with genetic faults, or mutations, in a gene called POLG. This gene provides the instructions needed to make a protein known as polymerase gamma, which is responsible for “reading” sequences of mitochondrial DNA (mtDNA) and using them as a template to produce more mtDNA within the mitochondria. If this protein doesn’t work properly due to mutations within the POLG gene, this can lead to a reduction in the amount or quality of mtDNA in affected tissues, which in turn can lead to a number of different POLG-related mitochondrial diseases. These include Alpers syndrome, chronic progressive external ophthalmoplegia (CPEO) and Leigh syndrome.
As with nearly every mitochondrial disease, the clinical features of POLG-related disease can be very different among patients. But there are some clinical features that are described more often than others. These include movement disorders, a group of neurological conditions that cause abnormal movement, and so the aim of the study was to describe the range of different movement disorders seen in children with POLG mutations. In addition, the study also investigated the levels of certain chemical messengers, or neurotransmitters, present in fluid taken from the spinal cord to try and identify a specific profile that could be linked to POLG-related disease.
The researchers found that almost half of the patients with a confirmed POLG mutation had evidence of a movement disorder, with a wide range of different abnormal movements often seen as the prominent feature of the disease. Moreover, these movement disorders were sometimes seen before the onset of other clinical features, which led the authors to recommend that clinicians consider POLG disease in children who initially present with abnormal movement, particularly when associated with neurodevelopmental delay, regression or epilepsy.
The study also revealed that although children with POLG-related disease can display abnormal levels of certain neurotransmitters in their spinal fluid, there did not appear to be a specific neurotransmitter that was abnormal in every patient tested. Despite this, the results of the study did appear to suggest that this kind of ‘neurotransmitter analysis’ might be a helpful tool when considering the possibility of POLG disease in affected patients, although it would require a larger cohort to determine the full potential of this in terms of diagnostic use.
Studies such as this are important for improving the diagnosis of mitochondrial disease, which is one of our aims at The Lily Foundation. This requires the commitment and dedication of many people, including the mitochondrial specialists who we continue to work closely with to improve the lives of those affected by mitochondrial disease.
The full article can be viewed here.