I have seen several patients with leukoencephalopathy and biochemical markers highly suggestive of mitochondrial disease. However, in most of these cases the mtDNA sequencing was non-diagnostic,  and I find it difficult to determine how to approach testing for the nuclear genes in these cases. However sometimes the MRI imaging can point towards right direction.  Steenweg et al., in a recent issue of Brain (2012:135; 1387-1394) describe mutations in EARS2, the gene encoding mitochondrial glutamyl-tRNA synthetase, in 12 patients with symmetrical cerebral white matter, thalamus, midbrain, pons, medulla and cerebellum lesions. Interestingly, these patients subdivide into a severe and mild group, the latter of which shows some level of recovery.

Hilary Vernon MD PhD

http://dx.doi.org/10.1036/ommbid.133