Description:

The brain is the organ primarily affected by elevated phenylalanine (Phe) in the disease phenylketonuria (PKU). The hallmark neuropathology of both the untreated and treated PKU brains is hypomyelination or demyelination or both. Because cognitive deficits are present in untreated and treated individuals, the link between the observed neuropathology and cognitive deficits is important to ascertain. Two current models of the molecular events underlying the cognitive deficits are presented. The first model is based on the hypothesis that cognitive deficits in individuals with PKU result from a deficiency of the neurotransmitter dopamine. Decreased levels of tyrosine in the PKU brain are believed to cause the low levels of dopamine. The possible connections between reduced dopamine levels and the observed myelin deficits are presented. However, as discussed, the link between the two remains elusive. The second model is based on the hypothesis that the primary insult to the PKU brain is loss of myelin and that this secondarily leads to neuronal dysfunction. The function of myelin is reviewed, including evidence showing that myelin and the axon communicate with one another to form a functional unit. Because the ability of the axon to conduct action potentials at normal speed is compromised when myelin is not formed or is lost, the latter model has the capacity to account for both abnormalities and cognitive deficits. Current studies characterizing the neuropathology of the recently developed genetic mouse model for PKU, the PAHenu2 mouse, are reviewed. Preliminary evidence is summarized that indicates that Phe specifically inhibits cholesterol metabolism in the oligodendrocyte, the cell that forms myelin in the brain.

Careful weaning is particularly important in phenylketonuria (PKU). Dietary phenylalanine intake is severely restricted, and the diet is supplemented with phenylalanine-free amino acids and special low protein foods. In PKU, there are no evidence-based weaning guidelines and no studies assessing the introduction of solid foods. We critically review the literature and examine current UK weaning practices. Ideally, weaning in PKU should closely reflect the ‘model’ for healthy infants. However, the requirement for optimal blood phenylalanine control and the demands of diet therapy overshadow the social aspects of weaning. Solid food intake is established with very low protein foods first, and then 50mg phenylalanine exchanges (equivalent to 1g of intact protein) gradually replace breast/formula feeds. Introducing solids before the recommended 6 months of age may be advantageous because there is a less persistent neophobic food response, possibly leading to better food acceptance. Infants with PKU also require a special phenylalanine-free protein substitute. Between 6 and 12 months, a second concentrated source of phenylalanine-free protein substitute is required. This is commonly given as an additional liquid, although the prescribed volume may adversely affect appetite. Alternatively, a second-stage protein substitute administered as a paste may better suit feeding development. Further research aiming to examine the weaning process in PKU with a focus on biological, maternal, infant, social and environmental factors is required. This will help provide evidence for the effect of protein substitute on appetite and help in the development of evidence-based guidelines.

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With Regards

Catirin
Journal Coordinator
Global Journal of Research and Review