- Unexplained multi-system progressive disorder usually involving the central nervous system and/or neuromuscular system
- Contributory laboratory findings may include but are not restricted to:
- Characteristic brain MR imaging, e.g. brainstem or basal ganglia involvement, infarction not confined to typical vascular territory, leukoencephalopathy
- Raised serum, CSF or urinary organic acid biomarkers (e.g. lactate, 3-MGA)
- Evidence of mitochondrial dysfunction in diagnostic biopsies including histochemical (COX-deficient fibres, ragged-red fibres) and biochemical (respiratory chain enzyme deficiencies) markers of disease pathology.
- Mitochondrial DNA and common nuclear genetic causes (e.g. POLG) excluded (m.3243A>G, POLG)
Prior genetic testing guidance
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition.
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.
PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.
Prior genetic testing genes
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:
- Mitochondrial DNA
- Common nuclear genetic causes as appropriate
These requirements will be kept under continual review during the main programme and may be subject to change.