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.

中文翻译：

---

苯丙酮尿症的白质紊乱：可能的潜在机制

白质病变以及智力障碍、小头畸形和其他中枢神经系统损伤是通常归因于典型苯丙酮尿症 (PKU) 的临床特征。PKU是一种由苯丙氨酸羟化酶缺乏引起的遗传性代谢疾病。l累积苯丙氨酸 (Phe) 及其代谢物存在于苯丙酮尿症患者的组织和体液中。为了减轻临床发现，严格的膳食 Phe 限制构成了 PKU 治疗管理的核心。髓鞘形成是少突胶质细胞将髓鞘包裹在轴突周围的过程，支持动作电位的传导。白质损伤与 PKU 相关的脑损伤有关，尤其是在未经治疗或治疗不当的患者中。本综述总结了有关驱动 PKU 患者白质病理的推定机制的证据。