Jameson Elisabeth, Remmington Tracey
Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Department of Women's and Children's Health, University of Liverpool, Liverpool, UK.
Cochrane Database Syst Rev. 2020 Jul 16;7(7):CD001304. doi: 10.1002/14651858.CD001304.pub3.
Phenylketonuria is an inherited disease treated with dietary restriction of the amino acid phenylalanine. The diet is initiated in the neonatal period to prevent learning disability; however, it is restrictive and can be difficult to follow. Whether the diet can be relaxed or discontinued during adolescence or should be continued for life remains a controversial issue, which we aim to address in this review. This is an updated version of a previously published review.
To assess the effects of a low-phenylalanine diet commenced early in life for people with phenylketonuria. To assess the possible effects of relaxation or termination of the diet on intelligence, neuropsychological outcomes and mortality, growth, nutritional status, eating behaviour and quality of life.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Most recent search of the Inborn Errors of Metabolism Trials Register: 30 April 2020.
All randomised or quasi-randomised controlled trials comparing a low-phenylalanine diet to relaxation or termination of dietary restrictions in people with phenylketonuria.
Two authors independently assessed study eligibility and methodological quality, and subsequently extracted the data.
We included four studies in this review (251 participants), and found few significant differences between treatment and comparison groups for the outcomes of interest. Blood phenylalanine levels were significantly lower in participants with phenylketonuria following a low-phenylalanine diet compared to those on a less restricted diet, mean difference (MD) at three months -698.67 (95% confidence interval (CI) -869.44 to -527.89). Intelligence quotient was significantly higher in participants who continued the diet than in those who stopped the diet, MD after 12 months 5.00 (95% CI 0.40 to 9.60). However, these results came from a single study.
AUTHORS' CONCLUSIONS: The results of non-randomised studies have concluded that a low-phenylalanine diet is effective in reducing blood phenylalanine levels and improving intelligence quotient and neuropsychological outcomes. We were unable to find any randomised controlled studies that have assessed the effect of a low-phenylalanine diet versus no diet from diagnosis. In view of evidence from non-randomised studies, such a study would be unethical and it is recommended that low-phenylalanine diet should be commenced at the time of diagnosis. There is uncertainty about the precise level of phenylalanine restriction and when, if ever, the diet should be relaxed. This should be addressed by randomised controlled studies; however, no new studies are expected in this area so we do not plan to update this review.
苯丙酮尿症是一种遗传性疾病，通过限制饮食中氨基酸苯丙氨酸的摄入来治疗。该饮食方案在新生儿期开始实施以预防学习障碍；然而，它具有限制性，可能难以坚持。在青春期饮食是否可以放宽或停止，还是应该终身持续，这仍然是一个有争议的问题，我们旨在通过本综述来探讨。这是之前发表的综述的更新版本。
评估早期开始的低苯丙氨酸饮食对苯丙酮尿症患者的影响。评估饮食放宽或终止对智力、神经心理结局、死亡率、生长、营养状况、饮食行为和生活质量的可能影响。
我们检索了Cochrane囊性纤维化和遗传疾病组试验注册库，其中包括通过全面电子数据库检索、相关期刊手工检索以及会议论文摘要集确定的参考文献。最近一次检索先天性代谢缺陷试验注册库的时间为2020年4月30日。
所有比较低苯丙氨酸饮食与放宽或终止苯丙酮尿症患者饮食限制的随机或半随机对照试验。
两位作者独立评估研究的纳入资格和方法学质量，随后提取数据。
我们在本综述中纳入了四项研究（251名参与者），发现治疗组和对照组在感兴趣的结局方面几乎没有显著差异。与饮食限制较少的参与者相比，苯丙酮尿症患者在采用低苯丙氨酸饮食后血液苯丙氨酸水平显著降低，三个月时的平均差值（MD）为-698.67（95%置信区间（CI）-869.44至-527.89）。继续饮食的参与者的智商显著高于停止饮食的参与者，12个月后的MD为5.00（95%CI 0.40至9.60）。然而，这些结果来自一项单一研究。作者结论：非随机研究的结果得出结论，低苯丙氨酸饮食在降低血液苯丙氨酸水平、提高智商和神经心理结局方面是有效的。我们未能找到任何评估从诊断开始低苯丙氨酸饮食与不饮食效果对比的随机对照研究。鉴于非随机研究的证据，这样的研究将是不道德的，建议在诊断时开始低苯丙氨酸饮食。关于苯丙氨酸限制的确切水平以及饮食是否应放宽（如果放宽的话）的时间存在不确定性。这应该通过随机对照研究来解决；然而，预计该领域不会有新的研究，因此我们不计划更新本综述。
