Kreiskliniken Reutlingen GmbH, Reutlingen, Germany.
Mol Genet Metab. 2011;104 Suppl:S26-30. doi: 10.1016/j.ymgme.2011.08.025. Epub 2011 Aug 26.
The problem to evaluate treatment outcome in adult PKU (phenylketonuric) patients lies in the heterogeneity of the adult PKU population. This heterogeneity is not only based on the different treatment history of every individual patient but also on the different severity of the underlying defect of the enzyme phenylalanine hydroxylase. Recent, partly double blind studies in adult PKU patients further support recommendation for lifelong treatment. However, it has become evident that dietary treatment is suboptimal and continuation to adulthood often not accepted. Late detected PKU patients (up to 4-6 years of age) benefit from strict dietary treatment and are able to catch up in intellectual performance. Untreated, severely retarded patients with behavioral changes may benefit from introduction of dietary treatment. However, individual decision is necessary and based on the personal situation of the patient. In early and well treated patients a number of studies have demonstrated that cognitive and neurosychologic tests are different from controls. In addition there is evidence that patients with higher blood phenylalanine (phe) levels demonstrate more often psychiatric symptoms like depression and anxiety. Medical problems are more often observed: there are certain risks as impaired growth, decreased bone mineral density and nutrional deficits probably caused by dietary treatment with an artificial protein substitute and/or missing compliance with an unpleasant diet. The long term risk of a strict dietary treatment must be balanced with the risk of higher blood phe (mean blood phenylalanine >600-900 μmol/L) on cognitive and neuropsychological functions and psychiatric symptoms. Further studies should consider the role of blood phe exposure for brain development in childhood and for brain function in all ages. Besides mean blood phe, fluctuation of blood phe over time is important. Fluctuation of blood phe is decreased by sapropterin treatment in responsive patients which would on the long term may have positive effects on cognitive outcome. Further studies also should include adult PKU patients.
评估成年苯丙酮尿症（PKU）患者治疗效果的问题在于成年 PKU 患者群体的异质性。这种异质性不仅基于每个患者不同的治疗史，还基于苯丙氨酸羟化酶潜在缺陷的严重程度不同。最近，对成年 PKU 患者进行的部分双盲研究进一步支持了终身治疗的建议。然而，人们已经意识到，饮食治疗并不理想，成年后往往无法接受。晚期发现的 PKU 患者（高达 4-6 岁）受益于严格的饮食治疗，并能够在智力表现上迎头赶上。未经治疗、行为改变严重的智力迟钝患者可能受益于饮食治疗的引入。然而，个体决策是必要的，并且基于患者的个人情况。在早期和治疗良好的患者中，许多研究已经证明认知和神经心理学测试与对照组不同。此外，有证据表明，血苯丙氨酸（phe）水平较高的患者更常出现抑郁和焦虑等精神症状。更容易观察到医疗问题：存在一定的风险，如生长受损、骨密度降低和营养不足，这可能是由于饮食治疗中使用人工蛋白质替代品和/或不遵守令人不快的饮食造成的。严格饮食治疗的长期风险必须与高血 phe（平均血 phe ＞600-900μmol/L）对认知和神经心理学功能及精神症状的风险相平衡。进一步的研究应考虑血 phe 暴露对儿童期大脑发育和所有年龄段大脑功能的作用。除了平均血 phe 外，血 phe 随时间的波动也很重要。在有反应的患者中，sapropterin 治疗可降低血 phe 的波动，从长远来看，这可能对认知结果产生积极影响。进一步的研究还应包括成年 PKU 患者。
