Dietary interventions for phenylketonuria

 

Abstract

Background

Phenylketonuria is an inherited disease treated with dietary restriction of the amino acid phenylalanine. The diet is initiated in the neonatal period to prevent mental handicap; 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.

Objectives

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.

Search methods

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: 05 March 2009.

Selection criteria

All randomised or quasi-randomised controlled trials comparing a low-phenylalanine diet to relaxation or termination of dietary restrictions in people with phenylketonuria.

Data collection and analysis

Two authors independently assessed study eligibility and methodological quality, and subsequently extracted the data.

Main results

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.

 

Plain language summary

Using diet to manage phenylketonuria

Phenylketonuria (PKU) is an inherited disease that affects the breakdown of protein. High levels of the amino acid phenylalanine in the blood damage the nervous system and can also lead to mental handicap. Newborn babies with PKU are given a special diet low in phenylalanine. Other studies suggest that a low-phenylalanine diet can reduce blood phenylalanine levels. The review includes four studies, but we were not able to combine many results. Results from one study showed that blood phenylalanine levels were lower and intelligent quotient higher for people on a special diet. We recommend that a low-phenylalanine diet should be followed from the time of diagnosis. More research is needed to show if it is safe to relax this diet later on.

 

摘要

背景

苯酮尿症飲食治療評估

苯酮尿症為一可經由嚴格控制飲食中苯丙胺酸的攝取，而獲得治療成效的先天代謝異常的遺傳疾病。在新生兒期即開始進行飲食治療的控制，將能有效避免智能障礙的問題發生，然而嚴格的低蛋白飲食控制並不容易遵行。 低蛋白飲食控制應該遵行終身；或是等到了成年期即可豁免，一直是頗受爭議的議題，此篇評論即是針對此一議題進行探討。

目標

研究對象為在幼年時期即接受低蛋白飲食治療的苯酮尿症患者，以評估他們在放鬆或停止飲食控制後，對智力、神經心理表現、生命的威脅(致死性)、生長情形、營養狀態、飲食行為及生活品質等各方面影響。

搜尋策略

我們搜尋Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register ，其中包括由廣泛的資料庫所找出的參考文獻、人工搜尋相關期刊、研討會摘要手冊。最近一次搜尋先天性代謝異常(inborn errors of metabolism)試驗登錄中心日期為：2009年3月5日。

選擇標準

選取所有以隨機對照試驗(randomised controlled trials)或近隨機對照試驗(quasirandomised controlled trials)，比較已經放鬆或停止飲食控制之苯酮尿症患者，及仍採低苯丙胺酸的飲食控制之苯酮尿症患者，所得的研究成果。

資料收集與分析

兩位作者各自獨立的評估這些研究的適切性，及其研究方法上的品質，以及接下來資料的選用及分析。

主要結論

在這篇評論中，我們包括了4篇研究(251位研究對象)，並在治療組及對照組之間發現少數顯著的差異。 首先，從血中苯丙胺酸的數值來看，仍採飲食控制的對照組，數值顯著的低於已放鬆或停止飲食控制的實驗組，三個月間數值的加權平均變化數(weighted mean difference, WMD)為 −698.67(95%的信心區間為 −869.44至 −527.89)。 在智力(IQ)的比較上來看，仍採飲食控制的對照組，IQ顯著高於已放鬆或停止飲食控制的實驗組，十二個月間的加權平均變化數則為5(95%的信心區間為0.4到9.6)；唯上述研究結果為來自單一的研究結果。

作者結論

經由上述非隨機對照試驗所得的結果發現，低苯丙胺酸的飲食控制有助於降低血中苯丙胺酸的數值，並改善智力及神經心理學上的表現。 在文獻查詢上，我們未發現有將苯酮尿症患者分為接受及未接受飲食控制的隨機分組研究，根據非隨機分組研究的觀點，進行隨機分組研究並不符合醫學倫理，因為這些病人應該在診斷初始便接受低苯丙胺酸飲食。目前對於苯丙胺酸值的控制目標，以及飲食治療可以放鬆的時機並無定論。答案可能仍須經隨機分組研究後才有結論。

翻譯人

本摘要由臺灣大學附設醫院蕭雅慧翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

在苯酮尿症患者嬰幼兒時期即進行低苯丙胺酸的飲食治療，將能避免或減少患者智能障礙的發生，但飲食治療該持續多久，還需要有更多研究來闡明。苯酮尿症為蛋白質代謝異常的遺傳性疾病，血中過高無法代謝的苯丙胺酸，將損害中樞神經系統，進而導致智能障礙的發生，因此當新生兒一確診為此症，即應予以低苯丙胺酸的飲食治療。先前研究建議，低苯丙胺酸飲食能有效降低血中苯丙胺酸的數值，然而在孩童較大或成年時放鬆飲食治療的控制是否合宜，仍需更多的研究來提供論證。