caa a22 4500 475785681 CHVBK 20180406123657.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/PL00014371 doi (NATIONALLICENCE)springer-10.1007/PL00014371 Huttenlocher Peter R. Department of Pediatrics MC 3055, University of Chicago, Chicago, IL 60637, USA e-mail: phutten@peds.bsd.uchicago.edu Tel.: +1-773-7026487; Fax: +1-773-7024786, US aut The neuropathology of phenylketonuria: human and animal studies [Elektronische Daten] [Peter R. Huttenlocher] Pathologic changes in the brain of untreated phenylketonuria (PKU) patients occur in structures that develop post-natally, i.e. in myelination of subcortical white matter and spinal cord and in the growth of axons, dendrites and synapses in cerebral cortex. In addition, a small minority of brains show evidence of progressive white matter degeneration (leucodystrophy). The pathologic changes are thought to be due to toxic effects of phenylalanine and/or its metabolites. It is assumed that they can be prevented by dietary therapy during infancy and childhood, but direct confirmation by neuropathologic studies is lacking. The recently discovered genetic mouse mutant Pahenu2 provides an excellent animal model in which effects of PKU on brain development, including dendritic and synaptic development in cerebral cortex, can be assessed. In human PKU, there needs to be neuropathologic study of the brains from PKU patients, particularly adults, with a history of dietary therapy. Special attention needs to be paid to the study of white matter in such cases, in view of recent reports of white matter lesions on MRI despite dietary treatment. Conclusion Careful correlation is needed between neuropathology, magnetic resonance imaging white matter changes, dietary history and clinical findings. Finally, neuropathologic investigation is needed to determine whether progressive degeneration of the white matter (leucodystrophy) poses a risk to adults in whom dietary therapy has been discontinued. Springer-Verlag Berlin Heidelberg, 2000 Key words Developmental arrest nationallicence Dysmyelination nationallicence Leucodystrophy nationallicence Neuropathology nationallicence Phenylketonuria nationallicence Neuropathology nationallicence AbbreviationPKU phenylketonuria nationallicence https://doi.org/10.1007/PL00014371 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00014371 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Huttenlocher Peter R. Department of Pediatrics MC 3055, University of Chicago, Chicago, IL 60637, USA e-mail: phutten@peds.bsd.uchicago.edu Tel.: +1-773-7026487; Fax: +1-773-7024786, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer