White matter involvement is a common manifestation of mitochondrial encephalopathy, often due to defects in mitochondrial genes or nuclear genes. The classical mitochondrial diseases caused by mutations in mitochondrial genes are MELAS, Leigh and KSS. Respiratory chain complexes I,II,V often cause Leigh, most of which are due to nuclear gene defects, resulting in a group of clinical manifestations of early onset white matter encephalopathy. Defects in nuclear genes that maintain the integrity and copy number of mitochondrial genes can also manifest clinically as white matter brain involvement. Examples include MNGIE due to TYMP gene defects, and MPV17 gene defects.