[SOLUTION] Mitochondrial Encephalopathy

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1. How can you explain the observation that, even within the same family, patients
with the A3243G mutation may manifest very different severity of symptoms?
2. Why would a physician recommend avoiding fasting or to eat multiple smaller meals
during the day rather than the traditional three meals?
3. Some pediatric patients with MELAS react badly when they are immunized against
common childhood diseases. Can you suggest a reason why vaccination may exacerbate
MELAS symptoms?
4. Which of the respiratory complexes would you expect to be least affected by mutations
in mtDNA?
5. Although many mitochondrial diseases, such as MELAS, will involve multiple organs,
neurological or neuromuscular abnormalities are often the earliest signs of disease. Why?
6. Why does the A3243G mutation associated with MELAS lead to reduced activity of
Human Structure and Function GMS 6604 page 13
respiratory complexes I and IV, while the point mutation at 11778 (within the ND4 gene)
associated with Leber’s hereditary optic neuropathy affects only respiratory complex I?
7. Vitamin C (ascorbate) enhances the ab sorption of iron from the intestines. For this
reason, it is recommended that vitamin C not be administered to a patient with MELAS
immediately prior to or subsequent to a meal of red meat o r other foods rich in iron.
What is the biochemical basis for the concern about increased iron availability to a patient with

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