Congenital brain malformations in mitochondrial disease

Abstract

The majority of patients with mitochondrial disease have some degree of neuropathology and this is usually degenerative in nature. However, in a subset of mitochondrial diseases there are additional specific and characteristic congenital malformations in the brain. These developmental abnormalities are not unique to mitochondrial diseases and their association with only some conditions suggests that they are not simply due to energy deprivation or accumulation of metabolites such as lactic acid. Pathogenic mechanisms are at present unknown, but interference with neurotransmitter homeostasis, in addition to altered energy metabolism, may be important. The postnatal evolution of the neuropathology in these conditions and the type and pattern of the malformations suggest secondary degeneration of specific brain structures during fetal life rather than primary interference with developmental pathways.