Location of defect: mitochondrial DNA (mtDNA) near nucleotide 3243
Effect: respiratory chain enzyme deficiency with defective oxidative phosphorylation
Inheritance: non-Mendelian, either sporadic or through maternal pedigree
Onset: typically under the age of 20
Key features:
(1) mitochondrial myopathy, with red ragged fibers on Gomori trichrome stain
(2) encephalopathy
(3) lactic acidosis
(4) stroke-like episodes in a non-vascular distribution (associated with microvascular damage)
CNS findings may include:
(1) seizures
(2) agitation
(3) hallucinations
(4) generalize asthenia
(5) migraine-like headaches
(6) cognitive dysfunction
Additional findings may include:
(1) diabetes mellitus
(2) hypothalamo-pituitary dysfunction
(3) focal segmental glomerulosclerosis
(4) ophthalmoplegia
(5) hypertrophic cardiomyopathy
(6) gastrointestinal dysmotility
