The neuropathology of phenylketonuria: human and animal studies
The neuropathology of phenylketonuria: human and animal studies
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DOI：
10.1007/pl00014371
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发表时间：
2000-10-01
影响因子：
3.6
通讯作者：
Huttenlocher, PR
中科院分区：
文献类型：
--
作者：
Huttenlocher, PR
未经治疗的苯丙酮尿症（PKU）患者的脑中的病理变化发生在出生后发育的结构中，即在皮质下白色物质和脊髓的髓鞘形成中以及在大脑皮质中轴突、树突和突触的生长中。此外，少数大脑显示出进行性白色物质变性（脑白质营养不良）的证据。病理变化被认为是由于苯丙氨酸和/或其代谢产物的毒性作用。一般认为，在婴儿和儿童时期可以通过饮食治疗来预防，但缺乏神经病理学研究的直接证实。最近发现的基因突变小鼠pah（enu 2）提供了一个很好的动物模型，其中PKU对大脑发育的影响，包括大脑皮层中的树突和突触发育，可以评估。在人类PKU中，需要对PKU患者的大脑进行神经病理学研究，特别是有饮食治疗史的成年人。需要特别注意的是，在这种情况下的白色物质的研究，鉴于最近的报告，白色物质病变的MRI，尽管饮食treatment.Conclusion仔细相关的神经病理学，磁共振成像白色物质的变化，饮食史和临床表现。最后，还需要进行神经病理学检查，以确定白色物质的进行性变性（脑白质营养不良）是否对停止饮食治疗的成人构成风险。
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 axone, 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 pah(enu2) 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.