Objective:

To identify patterns of white matter involvement in mitochondrial disease.

Background:

Mitochondrial disease has been estimated to affect 1 in 4300 individuals. Primary mitochondrial diseases (PMD) are caused by pathogenic variants in >300 genes. PMD can present at any age with an average of 16 multi-systemic symptoms per patient and often involves the neurological system due to its high metabolic demand. There is limited knowledge regarding mitochondrial leukoencephalopathies. In this study, we reviewed patterns of white matter involvement on MRI in patients with genetically confirmed PMD. 

Design/Methods:

Retrospective chart review of 186 patients with genetically confirmed PMD was conducted. MRI studies available for 153 patients were analyzed to identify presence of white matter involvement. Neuroimaging patterns were delineated based on location, type of involvement (leukodystrophy vs hypomyelination), T1 and T2 appearance, cystic changes, volume loss, atrophy, restricted diffusion, contrast enhancement and associated brain structure involvement. Information was collected regarding CSF protein level, plasma lactate level, and lactate peak on magnetic resonance spectroscopy.  

Results:

White matter involvement was observed in 61 out of 153 patients with MRI studies available to review. Genetic diagnosis of these patients included genes involved in mtDNA translation (C12ORF65, MRPS34, RMND1), mtDNA depletion (FBXL4), oxidative phosphorylation (AIFM1, EARS2, CARS2, FARS2, VARS2), complex I function (NDUFS1, NUBPL), complex II function (SDHB), complex IV function (SURF1), single large scale mtDNA deletion, mtDNA transcription (MT-TL1), pyruvate dehydrogenase complex (PDH, ECHS1, PDHA1) and thiamine transport (SLC19A3). Leukodystrophy pattern was seen in 14 while hypomyelination was observed in 16 patients. Location was periventricular in 23, diffuse in 15 and involving corpus callosum in 25 patients. Restricted diffusion was observed in 18, cystic changes in 10, volume loss in 14 and associated cerebral/cerebellar atrophy in 11 patients. 

Conclusions:

Leukoencephalopathy with specific imaging patterns in neurologically complex patients with multisystemic presentations should warrant detailed evaluation for mitochondrial disease.