Brain proton magnetic resonance spectroscopy showing reduced N-acetyl aspartate, normal creatine, and elevated lactate.
Elevated cerebral spinal fluid protein (> 100 mg/dL)
Cerebral volume loss (central > cortical, with ventriculomegaly) on repeat magnetic resonance imaging or computed tomography studies.
At least one electroencephalogram showing a multifocal paroxysmal activity with high-amplitude delta slowing (200 – 1000 microvolts) and spikes/polyspikes (10 – 100 microvolts, 12-25 Hertz).
Cortical blindness or optic atrophy.
Abnormal visual evoked potentials and normal electroretinogram.
Quantitative mitochondrial DNA depletion in skeletal muscle or liver (35% mean).
Deficiency in polymerase gamma enzymatic activity (≤ 10%) in skeletal muscle or liver.
Elevated blood or cerebral spinal fluid lactate (3 mM) on at least one occasion in the absence of acute liver failure.
Isolated complex IV or a combination I, III, and IV electron transport complex defects (≤ 20% of normal) upon liver respiratory chain testing.
A sibling confirmed to have Alpers-Huttenlocher syndrome.