University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
J Inherit Metab Dis. 2012 Nov;35(6):983-92. doi: 10.1007/s10545-012-9458-1. Epub 2012 Mar 6.
Tetrahydrobiopterin (BH(4))-sensitive phenylketonuria (PKU) can be treated with sapropterin dihydrochloride. We studied metabolic control and health-related quality of life (HRQoL) in PKU patients treated with BH(4).
Based on the review of neonatal BH(4) test results and mutation analysis in 41 PKU patients, 19 were identified as potentially BH(4)-sensitive (9 females, 10 males, age 4-18 years). We analyzed phenylalanine (phe) concentrations in dried blood samples, nutrition protocols, and HRQoL questionnaires (KINDL(®)) beginning from 1 year before, during the first 42 days, and after 3 months of BH(4) therapy.
Eight BH(4)-sensitive patients increased their phe tolerance (629 ± 476 vs. 2131 ± 1084 mg, p = 0.006) while maintaining good metabolic control (phe concentration in dried blood 283 ± 145 vs. 304 ± 136 μM, p = 1.0). Six of them were able to stop dietary protein restriction entirely. BH(4)-sensitive patients had average HRQoL scores that were comparable to age-matched healthy children. There was no improvement in HRQoL scores after replacing classic dietary treatment with BH(4) supply, although personal reports given by the patients and their parents suggest that available questionnaires are inappropriate to detect aspects relevant to inborn metabolic disorders.
BH(4) can allow PKU patients to increase their phe consumption significantly or even stop dietary protein restrictions. Unexpectedly, this does not improve HRQoL as assessed with KINDL(®), partly due to high scores even before BH(4) therapy. Specific questionnaires should be developed for inborn metabolic disorders.
四氢生物蝶呤（BH4）敏感型苯丙酮尿症（PKU）可以用沙丙蝶呤二盐酸盐治疗。我们研究了接受 BH4 治疗的 PKU 患者的代谢控制和健康相关生活质量（HRQoL）。
根据对 41 例 PKU 患者的新生儿 BH4 检测结果和突变分析的回顾，发现 19 例为潜在的 BH4 敏感型（9 名女性，10 名男性，年龄 4-18 岁）。我们分析了 19 例患者在接受 BH4 治疗前 1 年、治疗开始后 42 天内以及 3 个月后，干血斑中苯丙氨酸（phe）浓度、营养方案和 HRQoL 问卷（KINDL®）。
8 例 BH4 敏感型患者增加了 phe 的耐受量（629±476 vs. 2131±1084mg，p=0.006），同时保持了良好的代谢控制（干血斑phe 浓度 283±145 vs. 304±136μM，p=1.0）。其中 6 例患者能够完全停止饮食蛋白限制。BH4 敏感型患者的 HRQoL 评分与同龄健康儿童相当。尽管患者及其家长的个人报告表明，现有的问卷不适合检测与先天代谢紊乱相关的方面，但用 BH4 替代经典饮食治疗后，HRQoL 评分并没有改善。
BH4 可以使 PKU 患者显著增加 phe 的摄入量，甚至可以停止饮食蛋白限制。出乎意料的是，这并没有像 KINDL®评估的那样改善 HRQoL，部分原因是在接受 BH4 治疗之前评分就已经很高。应该为先天代谢紊乱开发专门的问卷。
