HDCN Article Review/Hyperlink

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)