Diagnostic Evaluation

Laboratory evaluation is a logical initial step in the diagnostic work up for suspected mitochondrial cytopathy.
Elevated lactate, although the sine qua non of most mito- chondrial diseases and MELAS in particular, is a nonspecific
marker of metabolic derangement of any cause. There are many other potential causes of lactic acidosis including
organic acidurias and aminoacidopathies, defects of the citric acid cycle, pyruvate dehydrogenase complex deficiency,
ischemia and hypoxemia, and, of course, laboratory error from improper handling of the specimen. Demonstration of an
elevated blood lactate level above 2.2 mmol/L is suggestive of a mitochondrial disorder, but the blood sample should be
free flowing, preferably arterial, and ana- lyzed immediately since there will be a spurious elevation if processing is
delayed. We typically obtain blood in the resting state but postexercise evaluation and post- prandial assessments might
be more sensitive. Blood lactate elevation is not spe- cific, and a normal blood lactate does not exclude the diagnosis of
MELAS. Lumbar puncture is an invaluable diagnostic tool and should be readily performed. Elevation of CSF lactate
above 2.2 mmol/L increases level of suspicion for MELAS. CSF lactate elevation is more sensitive than serum, but if
the fluid is bloody, a spurious elevation may occur and as such even CSF lactate elevation cannot be deemed entirely
sensitive nor specific.