Lotz-Havla Amelie S, Weiß Katharina, Schiergens Katharina, Regenauer-Vandewiele Stephanie, Parhofer Klaus G, Christmann Tara, Böhm Luise, Havla Joachim, Maier Esther M
Dr. von Hauner Children's Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Medical Department IV - Grosshadern, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Front Neurol. 2021 Dec 10;12:780624. doi: 10.3389/fneur.2021.780624. eCollection 2021.
In phenylalanine hydroxylase (PAH) deficiency, an easily feasible method to access the progression of neurodegeneration is warranted to contribute to current discussions on treatment indications and targets. The objective of the present study was to investigate whether optical coherence tomography (OCT) measures as markers of neurodegeneration differ between patients with PAH deficiency and healthy controls (HCs) according to phenotype and metabolic control. In this single-center cross-sectional study, 92 patients with different phenotypes of PAH deficiency [PAH deficiency not requiring treatment, early treated phenylketonuria (ETPKU), and late-diagnosed phenylketonuria (PKU)] compared with 76 HCs were examined using spectral-domain OCT. Indices of phenylalanine elevation and variability were correlated with OCT parameters. Late-diagnosed PKU patients showed reduced peripapillary retinal nerve fiber layer (pRNFL) thickness and combined ganglion cell and inner plexiform layer (GCIPL) volume. Adult ETPKU patients were found to have lower GCIPL volume ( = 0.016), which correlated with the indices of phenylalanine control. In pediatric ETPKU patients with poor metabolic control, pRNFL was significantly reduced ( = 0.004). Patients with PAH deficiency not requiring treatment did not exhibit retinal degeneration. Inner nuclear layer (INL) was significantly increased in the pediatric ETPKU patients, driven by those with current poor metabolic control ( = 0.006). Our data provide evidence of retinal neuroaxonal degeneration and INL swelling, depending on the phenotype, current age, and metabolic control. These findings suggest that OCT is suitable to investigate neurodegeneration in PKU and we propose OCT as a sensitive, reliable, safe, low-burden, and low-cost examination for future multicenter studies.
在苯丙氨酸羟化酶（PAH）缺乏症中，需要一种易于实施的方法来了解神经退行性变的进展情况，以促进当前关于治疗指征和靶点的讨论。本研究的目的是调查作为神经退行性变标志物的光学相干断层扫描（OCT）测量结果在PAH缺乏症患者和健康对照（HC）之间是否因表型和代谢控制情况而有所不同。在这项单中心横断面研究中，使用光谱域OCT对92例不同表型的PAH缺乏症患者[不需要治疗的PAH缺乏症、早治疗苯丙酮尿症（ETPKU）和晚诊断苯丙酮尿症（PKU）]与76例HC进行了检查。苯丙氨酸升高和变异性的指标与OCT参数相关。晚诊断的PKU患者表现出视乳头周围视网膜神经纤维层（pRNFL）厚度降低以及神经节细胞和内网状层（GCIPL）体积减小。发现成年ETPKU患者的GCIPL体积较低（ = 0.016），这与苯丙氨酸控制指标相关。在代谢控制不佳的儿科ETPKU患者中，pRNFL显著降低（ = 0.004）。不需要治疗的PAH缺乏症患者未表现出视网膜变性。儿科ETPKU患者的内核层（INL）显著增加，这是由当前代谢控制不佳的患者导致的（ = 0.006）。我们的数据提供了视网膜神经轴突变性和INL肿胀的证据，这取决于表型、当前年龄和代谢控制情况。这些发现表明OCT适用于研究PKU中的神经退行性变，并且我们建议将OCT作为一种敏感、可靠、安全、低负担且低成本的检查方法用于未来的多中心研究。
