1. Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes (MELAS)

2. What is MELAS? Mitochondrial = Mutation in the mitochondria Encephalo- = Occurs in the head Myopathy = General term for muscle disease Lactic Acidosis = The blood gets too acidic Stroke-like Episodes = Brain-related symptoms of bleeding or blockage

3. Characteristics It is the most common maternally inherited mitochondrial disease Clinical Features: Strokes, myopathy, muscle twitching, dementia, and deafness To a lesser extent: vomiting, migrainelike headaches, diabetes, droopy eyelids, muscle weakness, and short stature

4. More Characteristics MELAS affects no specific race or gender more so than others Presentation of the disease occurs with the first stroke-like episode (usually 14-15 yrs of age) This is a progressive disorder with a high mortality rate

5. How does MELAS work? Abnormal mitochondria do not metabolize pyruvate Excess pyruvate is reduced to lactic acid which accumulates in blood and other fluids Large clumps of abnormal mitochondria form in the walls of small arteries and capillaries in the brain and muscles

6. What causes MELAS? There are at least 6 different point mutations associated with MELAS 80% of cases have a A to G point mutation in the tRNA (Leu) gene at bp 3243 7.5% of cases have a T to C point mutation in the tRNA (Leu) gene at bp 3271

8. Causes (contd.) All of these mutations are heteroplasmic Heteroplasmic = within a single cell, there is a mixture of mitochondria, some containing mutant DNA and some containing normal DNA This feature of mitochondrial diseases might offer a solution to the varied rates of progression and onset of the disease

9. References Scaglia, Fernando, MD. MELAS Syndrome. http://www.emedicine.com/ped/topic1406. htm. October 26, 2004 http://www.emedicine.com/ped/topic1406. htm http://herkules.oulu.fi/isbn9514255674/htm l/graphic33.gifhttp://herkules.oulu.fi/isbn9514255674/htm l/graphic33.gif