We report two novel mDNA mutations in the cytochrome b gene associated with complex III deficiency in two patients with developmental brain abnormalities.
Patient #1. Six year old boy with history of developmental delay, myalgias, muscle weakness, high CK, Wolff-Parkinson-White syndrome and increased lactate in brain on MRI underwent muscle biopsy that revealed early red ragged fibers (RRF). He died in sleep at the age of 21. Post mortem revealed accumulation of mitochondria in skeletal muscles, diaphragm and myocardium. The brain showed foci of heterotopic neurons and acellular patches of synaptophysin immunoreactivity in the white matter, and meningeal grey matter heterotopia.
Patient #2. This microcephalic girl was prematurely born blind and deaf at the 27th gestational week. She developed seizures at six months followed by spasticity, decorticate posturing, clonus, and progressive respiratory failure. She died at the age of five. Neuronal heterotopia were present throughout the white matter. Many small vessels showed hyalinosis and subendothelial calcifications. Cerebellum was atrophic and olivary nuclei depopulated.
Although our patients had identical mDNA mutation, they displayed striking difference in the severity of manifestations as well as neuropathological abnormalities, to a large extent proportional to the degree of mitochondrial heteroplasmy. Both individuals showed common denominator of variably expressed abnormities of the neuronal migration resulting in cortical mild microdysgenesis and wide-spread neuronal heterotopia in the white matter.
Conflictsof Interest:
None.
