MELAS (
mitochondrial encephalopathy with
lactic acidosis and
stroke-like episodes) is a maternally inherited disorder characterized by recurrent
cerebral infarctions that do not conform to discreet vascular territories. Here we report on a patient who presented at 7 years of age with
loss of consciousness and severe
metabolic acidosis following
vomiting and
dehydration. She developed progressive
sensorineural hearing loss,
myopathy, ptosis, short stature, and mild developmental delays after normal early development. Biochemical testing identified metabolites characteristic of
medium-chain acyl-CoA dehydrogenase (
MCAD) deficiency (
hexanoylglycine and
suberylglycine), but also severe lactic acidemia (10-25 mM) and, in urine, excess of
lactic acid, intermediates of the citric cycle, and marked
ketonuria, suggesting
mitochondrial dysfunction. She progressed rapidly to develop temporary
cortical blindness. Brain imaging indicated generalized
atrophy, more marked on the left side, in addition to white matter alterations consistent with a
mitochondrial disorder. Magnetic resonance angiography indicated occlusion of the left cerebral artery with development of collateral circulation (
Moyamoya syndrome). This process worsened over time to involve the other side of the brain. A muscle biopsy indicated the presence of numerous ragged red fibers. Molecular testing confirmed compound heterozygosity for the common mutation in the MCAD gene (985A>G) and a second pathogenic mutation (233T>C).
MtDNA testing indicated that the muscle was almost homoplasmic for the 3243A>T mutation in
tRNALeu, with a lower mutant load (about 50% heteroplasmy) in blood and skin fibroblasts. These results indicate that
mitochondrial disorders may be associated with severe
vascular disease resulting in
Moyamoya syndrome. The contribution of the concomitant
MCAD deficiency to the development of the phenotype in this case is unclear.