Herenger Yvan, Maes Emmanuelle, François Laurent, Pasco Jeremy, Bouchereau Juliette, Pichard Samia, Ogier de Baulny Hélène, Schiff Manuel
Reference Center for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, Paris 75019, France.
Department of Medical Information and Public Health, University Hospital, Tours 37000, France.
Mol Genet Metab Rep. 2019 Jul 25;20:100498. doi: 10.1016/j.ymgmr.2019.100498. eCollection 2019 Sep.
Phenylketonuria (PKU) is a disorder of phenylalanine metabolism, characterized by a neurotoxic phenylalanine (Phe) accumulation, and treatable with a life-long Phe-restricted diet. Though early and continuously treated PKU (ETPKU) patients exhibit normal IQ, their cognitive outcome remains suboptimal. In this longitudinal study, we aimed at assessing the determinants of IQ subscales and quality of metabolic control in ETPKU children. We collected blood Phe levels, numbers of blood samples for Phe determination, parents' socio-professional categories and school achievement data of 39 classical and moderate ETPKU patients who underwent two cognitive evaluations performed by the same neuropsychologist (at 6.5 and 10y of mean age). We then sought to evaluate the determinants of 1) the changes in their IQ between the two testings (delta IQ) and 2) the quality of metabolic control (evaluated by the median Phe levels during the year before the second test) with multivariate regression analysis. Though in the normal range, mean total IQ slightly decreased between the two evaluations, and we observed a better verbal than performance outcome. Modeling the determining factors of the delta IQ, we found a significant influence of the number of blood samples (β = 0.46, 95%CI = 0.13 to 0.79, p < 0.01) and the moderate type of PKU (β = 12.40, 95%CI = 3.69 to 21.11, p < 0.01) on verbal outcome. We failed to find any determining factors that would statistically influence metabolic control. In conclusion, ETPKU cognitive outcome is influenced by a network of metabolic and environmental factors, which is not reflected by the sole metabolic control.
苯丙酮尿症（PKU）是一种苯丙氨酸代谢紊乱疾病，其特征是具有神经毒性的苯丙氨酸（Phe）蓄积，可通过终身限制苯丙氨酸饮食进行治疗。尽管早期持续治疗的苯丙酮尿症（ETPKU）患者智商正常，但其认知结果仍不尽人意。在这项纵向研究中，我们旨在评估ETPKU儿童智商子量表的决定因素以及代谢控制质量。我们收集了39例经典型和中型ETPKU患者的血苯丙氨酸水平、用于苯丙氨酸测定的血样数量、父母的社会职业类别以及学校成绩数据，这些患者接受了同一位神经心理学家进行的两次认知评估（平均年龄分别为6.5岁和10岁）。然后，我们通过多元回归分析来评估以下因素的决定因素：1）两次测试之间智商的变化（智商差值）；2）代谢控制质量（通过第二次测试前一年的苯丙氨酸水平中位数来评估）。尽管在正常范围内，但两次评估之间平均总智商略有下降，并且我们观察到语言能力比操作能力的结果更好。对智商差值的决定因素进行建模时，我们发现血样数量（β = 0.46，95%CI = 0.13至0.79，p < 0.01）和中度型苯丙酮尿症（β = 12.40，95%CI = 3.69至21.11，p < 0.01）对语言能力结果有显著影响。我们未能找到任何在统计学上影响代谢控制的决定因素。总之，ETPKU的认知结果受到代谢和环境因素网络的影响，而这并不能仅通过代谢控制来反映。
