Past murine studies of phenylketonuria (PKU) have documented significant effects on cerebellum at both the gross and cellular levels. The profile of neurocognitive and motor difficulties associated with early-treated PKU (ETPKU) is also consistent with potential cerebellar involvement. Previous neuroanatomical studies of cerebellum in patients with PKU, however, have yielded mixed results. The objective of the present study was to further examine potential differences in cerebellar morphometry between individuals with and without ETPKU. To this end, we analyzed high resolution T1-weighted MR images from a sample of 20 individuals with ETPKU and an age-matched comparison group of 20 healthy individuals without PKU. Measurements of whole brain volume, whole cerebellum volume, cerebellar gray matter volume, and cerebellar white matter volume were collected by means of semiautomatic volumetric analysis. Data analysis revealed no significant group differences in whole brain volume, whole cerebellar volume, or cerebellar white matter volume. A significant reduction in cerebellar gray matter volume, however, was observed for the ETPKU group compared to the non-PKU comparison group. These findings expand on previous animal work suggesting that cerebellar gray matter is impacted by PKU. It is also consistent with the hypothesis that the cognitive difficulties experienced by individuals with ETPKU may be related to disruptions in gray matter. Additional studies are needed to fully elucidate the timing and extent of the impact of ETPKU on cerebellum and the associated neurocognitive consequences.

过去对苯丙酮尿症 (PKU) 的小鼠研究已经记录了苯丙酮尿症 (PKU) 在总体水平和细胞水平上对小脑的显着影响。与早期治疗 PKU (ETPKU) 相关的神经认知和运动困难的特征也与潜在的小脑受累一致。然而，之前对 PKU 患者小脑的神经解剖学研究得出的结果好坏参半。本研究的目的是进一步检查患有和未患有 ETPKU 的个体之间小脑形态测量的潜在差异。为此，我们分析了 20 名患有 ETPKU 的个体样本和由 20 名不患有 PKU 的健康个体组成的年龄匹配对照组的高分辨率 T1 加权 MR 图像。通过半自动体积分析收集全脑体积、全小脑体积、小脑灰质体积和小脑白质体积的测量结果。数据分析显示全脑体积、全小脑体积或小脑白质体积没有显着的组间差异。然而，与非 PKU 对照组相比，ETPKU 组的小脑灰质体积显着减少。这些发现扩展了之前的动物研究，表明小脑灰质受到 PKU 的影响。这也与 ETPKU 患者所经历的认知困难可能与灰质破坏有关的假设相一致。需要更多的研究来充分阐明 ETPKU 对小脑影响的时间和程度以及相关的神经认知后果。