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Review
. 2021 Jan;99(1):349-360.
doi: 10.1002/jnr.24598. Epub 2020 Mar 6.

White matter disturbances in phenylketonuria: Possible underlying mechanisms

Bruna Klippel Ferreira  1 , Melissa Torres Rodrigues  2   3 , Emilio Luiz Streck  4 , Gustavo Costa Ferreira  1 , Patricia Fernanda Schuck  2   3
Affiliations
Review

White matter disturbances in phenylketonuria: Possible underlying mechanisms

Bruna Klippel Ferreira et al. J Neurosci Res. 2021 Jan.

Abstract

White matter pathologies, as well as intellectual disability, microcephaly, and other central nervous system injuries, are clinical traits commonly ascribed to classic phenylketonuria (PKU). PKU is an inherited metabolic disease elicited by the deficiency of phenylalanine hydroxylase. Accumulation of l-phenylalanine (Phe) and its metabolites is found in tissues and body fluids in phenylketonuric patients. In order to mitigate the clinical findings, rigorous dietary Phe restriction constitutes the core of therapeutic management in PKU. Myelination is the process whereby the oligodendrocytes wrap myelin sheaths around the axons, supporting the conduction of action potentials. White matter injuries are implicated in the brain damage related to PKU, especially in untreated or poorly treated patients. The present review summarizes evidence toward putative mechanisms driving the white matter pathology in PKU patients.

Keywords: central nervous system; l-phenylalanine; myelin; oligodendrocytes; phenylketonuria.

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References

REFERENCES

    1. Adler-Abramovich, L., Vaks, L., Carny, O., Trudler, D., Magno, A., Caflisch, A., … Gazit, E. (2012). Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria. Nature Chemical Biology, 8(8), 701-706. https://doi.org/10.1038/nchembio.1002
    1. Aggarwal, S., Yurlova, L., & Simons, M. (2011). Central nervous system myelin: Structure, synthesis and assembly. Trends in Cell Biology, 21, 585-593. https://doi.org/10.1016/j.tcb.2011.06.004
    1. Albrecht, J., Garbade, S. F., & Burgard, P. (2009). Neuropsychological speed tests and blood phenylalanine levels in patients with phenylketonuria: A meta-analysis. Neuroscience and Biobehavioral Reviews, 33, 414-421. https://doi.org/10.1016/j.neubiorev.2008.11.001
    1. Alejandre, M. J., Marco, C., Ramirez, H., Segovia, J. L., & Garcia-Peregrin, E. (1984). Lipid composition of brain myelin from normal and hyperphenylalaninemic chick embryos. Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 77, 329-332. https://doi.org/10.1016/0305-0491(84)90338-9
    1. Allison, D. W., Chervin, A. S., Gelfand, V. I., & Craig, A. M. (2000). Postsynaptic scaffolds of excitatory and inhibitory synapses in hippocampal neurons: Maintenance of core components independent of actin filaments and microtubules. Journal of Neuroscience, 20, 4545-4554. https://doi.org/10.1523/JNEUROSCI.20-12-04545.2000

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