Sheena Narine S2639527 PCB3023 ...

Sheena Narine
S2639527
PCB3023
04/19/09
Leigh’s Disease
Leigh’s disease is a very uncommon inherited neurometabolic disorder that is mainly characterized by deterioration of the central nervous system. In most cases, it is inherited as an autosomal recessive trait. This disorder primarily affects infants between three months and two years of age. In the early stages, symptoms of this disease include loss of head control and motor skills. Over time, it progresses quickly to other symptoms such as lack of muscle tone, and lactic acidosis, which may lead to impairment of kidney and respiratory function. Two main underlying causes of Leigh’s disease are a deficiency of pyruvate dehydrogenase and mutations of mitochondrial DNA.
Mitochondria are tiny structures that act as “powerhouses” of the cell, by supplying the cells with energy. One of the most important processes in mitochondria is the TCA cycle, or Krebs cycle. The TCA cycle produces most of the ATP necessary for maintenance of the cell. ATP is produced by chemically converting molecules of the chemical pyruvate into carbon dioxide, water, and ATP. The energy stored in ATP is then executed to carry out the metabolic activities of other cells. Pyruvate dehydrogenase (PDH) is an enzyme in the PDH complex that aids in the process of breaking down pyruvate. In Leigh’s disease, individuals are unable to produce the necessary amount of PDH required to break down pyruvate; therefore the cells cannot produce enough ATP to function correctly.
Individuals with Leigh’s disease may also have mitochondria that are unable to produce ATP due to irregular mutations that take place in the mitochondrial DNA. These mutations interfere with the sources that provide energy to cells in a region of the brain that plays a role in motor performance. Due to the constant lack of energy in these brain cells, the central nervous system is affected which leads to progressive deterioration of motor functions. Specific parts of the brain that are affected by this lack of ATP include the basal ganglia, brainstem, and cerebellum. The most common treatment for Leigh’s disease is thiamine or Vitamin B1; however, the prognosis for individuals with Leigh’s disease is poor.
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