Sapropterin therapy increases stability of blood phenylalanine levels in patients with BH4-responsive phenylketonuria (PKU)
Sapropterin therapy increases stability of blood phenylalanine levels in patients with BH4-responsive phenylketonuria (PKU)
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DOI：
10.1016/j.ymgme.2010.06.015
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发表时间：
2010-10-01
影响因子：
3.8
通讯作者：
Sullivan, Christine
中科院分区：
文献类型：
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作者：
Burton, Barbara K.;Bausell, Heather;Sullivan, Christine
最近的研究表明，血苯丙氨酸水平的变异性与智商呈负相关，并且与平均血苯丙氨酸水平相比，血苯丙氨酸水平是早期和持续治疗的苯丙酮尿症（PKU）患者智商的更好预测因子。这表明血苯丙氨酸的稳定性应该是PKU患者的治疗目标。本研究的目的是确定用沙丙蝶呤治疗BH 4反应性PKU患者是否会增加血液苯丙氨酸水平的稳定性。回顾性研究了在芝加哥儿童纪念医院的PKU诊所接受沙丙蝶呤治疗的所有患者的记录。如果患者在2至4周的挑战期间对沙丙蝶呤有反应，则将其纳入研究（治疗2周后血液苯丙氨酸水平降低至少25%，或者在检测时血液苯丙氨酸控制良好的患者中，治疗4周时饮食苯丙氨酸耐受性增加）。共有37例受试者符合入选条件（16例男性; 21例女性）;平均年龄为12.6岁（范围：1.5-32.0岁）。所有受试者的观察总数（苯丙氨酸水平）为1391，平均值为39/受试者（范围，13-96）。利用线性混合建模来估计开始沙丙蝶呤之前（前）和之后（后）的血液苯丙氨酸的方差。使用SAS 9.1进行似然比检验。通过该模型估计的苯丙氨酸的平均值和标准偏差分别为6.67 mg/dl（4.20）和5.16 mg/dl（3.78）。沙丙蝶呤给药后的平均水平显著降低（p=.0002）。苯丙氨酸的受试者内方差（平均值和SD）为：术前6.897（2.62）和术后4.799（2.19）。这两个方差显著不同，p= 0.0017。我们得出结论，沙丙蝶呤治疗的结果，在增加血液苯丙氨酸水平的稳定性。这种作用可能会改善BH 4反应性PKU患者的认知结果。(C)2010年爱思唯尔公司All rights reserved.
It has recently been demonstrated that variability in blood phenylalanine levels is inversely correlated with IQ and is a better predictor of IQ in early and continuously treated patients with phenylketonuria (PKU) than mean blood phenylalanine levels. This suggests that stability of blood phenylalanine should be a therapeutic goal in patients with PKU. The purpose of this study was to determine if treatment with sapropterin in patients with BH4-responsive PKU would increase the stability of blood phenylalanine levels. The records of all patients treated with sapropterin in the PKU Clinic at Children's Memorial Hospital in Chicago were examined retrospectively. Patients were included in the study if they were responsive to sapropterin during a 2- to 4-week challenge (reduction of blood phenylalanine level of at least 25% after 2 weeks of therapy or, in the case of patients with well-controlled blood phenylalanine at the time of testing, increased dietary phenylalanine tolerance by 4 weeks of treatment). A total of 37 subjects were eligible for inclusion (16 male; 21 female); the mean age was 12.6 years (range, 1.5-32.0). The total number of observations (phenylalanine levels) for all subjects was 1391 with a mean of 39 per subject (range, 13-96). Linear mixed modeling was utilized to estimate variances of the blood phenylalanine before (pre) and after (post) starting sapropterin. Likelihood ratio test was performed using SAS 9.1. Means and standard deviations for phenylalanine as estimated by the model were 6.67 mg/dl (4.20) and post 5.16 (3.78). The mean level post-sapropterin was significantly lower (p=.0002). The within-subject variances (mean and SD) of phenylalanine were: pre 6.897 (2.62) and post 4.799 (2.19). These two variances are significantly different with a p=.0017. We conclude that sapropterin therapy results in increased stability of blood phenylalanine levels. This effect is likely to improve cognitive outcome in BH4-responsive patients with PKU. (C) 2010 Elsevier Inc. All rights reserved.