Chinnery PF, Turnbull DM, Walls TJ, Reading PJ
Recurrent strokes in a 34-year-old man
Lancet
(Aug) 350:560 1997

Some stroke due to ischemic cardiovascular disease is heritable, and
differences in apolipoprotein E, heritable coagulopathies, and racial
variation in vascular disease may be operative, along with several
mitochondrial mutations (see DeGraba and
Penix for a review). Mitochondrial abnormalities cause
the
"MELAS" syndrome,
for Mitochondrial Encephalopathy, Lactic
Acidosis, and Stroke-like episodes. Symptoms
usually onset in childhood, but may begin in early adulthood or even
at a mature age. Diagnosis is by genetic testing. Most of the
mitochondrial cases are due to an A to G mutation of mitochondrial DNA
at nucleotide position 3243, in the transfer RNA (Leu(UUR)) gene,
although other mitochondrial DNA mutations can also cause the MELAS
syndrome. Even back in 1992,
Ciafaloni et al
emphasized that the percentage of mutations present in blood was lower
than in muscle.
In this paper, Chinnery et al describe a 34 year old man with
presentation of migraine-like headaches, episodes of transient visual
disturbance and hemiparesthesia, lactic acidosis, and bilateral
parieto-occipital infarcts on CT. There was no evidence of
coagulation disorder or premature vascular disease. MELAS syndrome
was suspected and blood sent for mitochondrial DNA analysis. The test
was negative.
Because of continued suspicion of MELAS syndrome, a muscle biopsy was
done which showed that 10% of fibers had a typical "ragged red"
appearance, and 1-2% of muscle fibers were negative for cytochrome C
oxidase. When mitochondrial DNA was evaluated on the muscle biopsy
sample, the typical A3243G MELAS mutation was found.
Comment: The message of the paper is to reiterate that blood
screening for mtDNA mutations alone is a poor test for MELAS syndrome;
when clinical suspicion is high, a muscle biopsy is often necessary.
(John T. Daugirdas, M.D., University of Illinois at
Chicago)