Mitochondrial complex I deficiency nuclear type 21 is caused by a mutation in the NUBPL gene on chromosome 14q12.
All patients had a characteristic leukoencephalopathic pattern on brain MRI. Initial studies showed confluent or multifocal cerebral white matter lesions, predominantly affecting the deep white matter while sparing the U-fibers and internal and external capsules. These white matter lesions progress to volume loss as if the cavitated white matter lesions have collapsed.
There were also signal abnormalities and swelling of the corpus callosum, with subsequent atrophy, that may be continuous with the white matter lesions. Signal abnormalities were present in the cerebellar cortex, but not in the deep white matter.
Later imaging of most patients showed improvement of the cerebral white matter and corpus callosum abnormalities, but worsening of the cerebellar abnormalities that progresses to atrophy with secondary pontine atrophy.
Reference:
1. Kevelam, S. H., Rodenburg, R. J., Wolf, N. I., Ferreira, P., Lunsing, R. J., Nijtmans, L. G., Mitchell, A., Arroyo, H. A., Rating, D., Vanderver, A., van Berkel, C. G. M., Abbink, T. E. M., Heutink, P., van der Knaap, M. S. NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern. Neurology 80: 1577-1583, 2013.