Small group 1 - Problem 1 Flashcards
A 3-year-old child had normal height and weight, but had a reduced head circumference (microcephaly). This child had a vocabulary of ~20 words and appeared to be grossly mentally retarded. Muscle tone was weak and coordination was poor. The history indicated that the child exhibited decreased movement during the 3rd trimester in utero and fed poorly after birth. At 7 months of age, the child was noted to have slow development of motor skills. Lactic acidosis was detected at 18 months. A number o
Predict the genetic enzyme deficiency that is present in this child and explain your choice.
The elevated lactate develops because in the absence of PDH activity, pyruvate will accumulate and be converted into lactate by LDH.
Explain the relationship of the mental retardation and motor dysfunction to this disorder.
Without PDH, pyruvate cannot be converted to acetyl coA, and the Krebs cycle/citric acid cycle can’t be used to generate ATP from glucose metabolism. Glucose metabolism is essential to maintain normal CNS function. The mental retardation and motor dysfunction probably occur because of the inability to maintain normal metabolism and ATP levels. The elevated lactate can also be neurotoxic.
Predict whether nutritional therapies would be successful in treating this patient. Explain your answer.
Although no treatment has been proven to have long-term benefit, administration of a high fat (ketogenic) diet has had some positive effects in limiting neural damage. The brain normally metabolizes glucose to pyruvate and then to CO2 and H2O to maintain ATP levels. If this is not possible because of a PDH deficiency, the brain can switch to ketone metabolism to generate a portion of the needed ATP. This will happen when ketones are high enough to be transported across the blood brain barrier. A high fat, ketogenic diet has been used to attempt to bypass the PDH enzyme. The metabolism of fatty acids would result in ketone production; ketones can be utilized by the brain. Fatty acids can be metabolized by many tissues other than the brain.
What type of poisoning can also produce an increase in the blood concentrations of lactate and pyruvate?
Arsenic poisoning, which is a medical condition caused by elevated levels of arsenic in the body and cause headaches, confusion, severe diarrhea, and drowsiness. In addition, arsenite inhibits PDH by preventing the lipamide derivative to cycle between the oxidized and reduced forms. Chelating agents that sequester the arsenic away from blood proteins should be beneficial.
