Somaraju Usha Rani, Merrin Marcus
Department of Biochemistry and Genetics, Trinity School of Medicine, Harmony Hall, Prospect, Kingstown, St.Vincent, Saint Vincent and The Grenadines, P. O. Box 1669.
Cochrane Database Syst Rev. 2010 Jun 16(6):CD008005. doi: 10.1002/14651858.CD008005.pub2.
Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most natural foods are excluded from diet and supplements are used to supply other nutrients. Recent publications report a decrease in blood phenylalanine concentration in some patients treated with sapropterin dihydrochloride. We examined the evidence for the use of sapropterin dihydrochloride to treat phenylketonuria.
To assess the safety and efficacy of sapropterin dihydrochloride in lowering blood phenylalanine concentration in people with phenylketonuria.
We identified relevant trials from the Group's Inborn Errors of Metabolism Trials Register. Last search:07 May 2010.We also searched ClinicalTrials.gov and Current controlled trials. Last search: 01 September 2009.We contacted the manufacturers of the drug (BioMarin Pharmaceutical Inc.) for information regarding any unpublished trials.
Randomized controlled trials comparing sapropterin with no supplementation or placebo in people with phenylketonuria due to phenylalanine hydroxylase deficiency.
Two authors independently assessed trials and extracted outcome data.
Two placebo-controlled trials were included. One trial administered 10 mg/kg/day sapropterin in 89 children and adults with phenylketonuria whose diets were not restricted and who had previously responded to saproterin.This trial measured change in blood phenylalanine concentration. The second trial screened 90 children (4 to 12 years) with phenylketonuria whose diet was restricted, for responsiveness to sapropterin. Forty-six responders entered the placebo-controlled part of the trial and received 20 mg/kg/day sapropterin. This trial measured change in both phenylalanine concentration and protein tolerance. Both trials reported adverse events. The trials showed an overall low risk of bias; but both are Biomarin-sponsored. One trial showed a significant lowering in blood phenylalanine concentration in the sapropterin group (10 mg/kg/day), mean difference -238.80 mumol/L (95% confidence interval -343.09 to -134.51); a second trial (20 mg/kg/day sapropterin) showed a non-significant difference, mean difference -51.90 mumol/L (95% confidence interval -197.27 to 93.47). The second trial also reported a significant increase in phenylalanine tolerance, mean difference18.00 mg/kg/day (95% confidence interval 12.28 to 23.72) in the 20 mg/kg/day sapropterin group.
AUTHORS' CONCLUSIONS: There is evidence of short-term benefit from using sapropterin in some patients with sapropterin-responsive forms of phenylketonuria; blood phenylalanine concentration is lowered and protein tolerance increased. There are no serious adverse events associated with using sapropterin in the short term.There is no evidence on the long-term effects of sapropterin and no clear evidence of effectiveness in severe phenylketonuria.
苯丙酮尿症是由苯丙氨酸羟化酶缺乏所致。通过饮食限制苯丙氨酸可使血苯丙氨酸浓度维持在较低水平。大多数天然食物被排除在饮食之外，需使用补充剂来提供其他营养物质。近期有文献报道，部分接受盐酸沙丙蝶呤治疗的患者血苯丙氨酸浓度有所下降。我们对使用盐酸沙丙蝶呤治疗苯丙酮尿症的证据进行了研究。
评估盐酸沙丙蝶呤降低苯丙酮尿症患者血苯丙氨酸浓度的安全性和有效性。
我们从该组织的先天性代谢缺陷试验注册库中识别出相关试验。最后检索时间：2010年5月7日。我们还检索了ClinicalTrials.gov和Current controlled trials。最后检索时间：2009年9月1日。我们联系了该药物的制造商（BioMarin制药公司）以获取任何未发表试验的信息。
比较盐酸沙丙蝶呤与未补充或安慰剂对因苯丙氨酸羟化酶缺乏所致苯丙酮尿症患者影响的随机对照试验。
两位作者独立评估试验并提取结果数据。
纳入了两项安慰剂对照试验。一项试验对89名饮食未受限且先前对沙丙蝶呤有反应的苯丙酮尿症儿童和成人给予每日10mg/kg的盐酸沙丙蝶呤。该试验测量了血苯丙氨酸浓度的变化。第二项试验对90名饮食受限的4至12岁苯丙酮尿症儿童进行筛查，以确定其对沙丙蝶呤的反应性。46名有反应者进入试验的安慰剂对照部分，接受每日20mg/kg的盐酸沙丙蝶呤。该试验测量了苯丙氨酸浓度和蛋白质耐受性的变化。两项试验均报告了不良事件。试验显示总体偏倚风险较低；但两项试验均由BioMarin赞助。一项试验显示盐酸沙丙蝶呤组（每日10mg/kg）血苯丙氨酸浓度显著降低，平均差值为-238.80μmol/L（95%置信区间为-343.09至-134.51）；第二项试验（每日20mg/kg盐酸沙丙蝶呤）显示差异不显著，平均差值为-51.90μmol/L（95%置信区间为-197.27至93.47）。第二项试验还报告，在每日20mg/kg盐酸沙丙蝶呤组中，苯丙氨酸耐受性显著增加，平均差值为18.00mg/kg/天（95%置信区间为12.28至23.72）。
有证据表明，在某些对沙丙蝶呤有反应型的苯丙酮尿症患者中，使用沙丙蝶呤有短期益处；血苯丙氨酸浓度降低，蛋白质耐受性增加。短期内使用沙丙蝶呤无严重不良事件。尚无关于沙丙蝶呤长期影响的证据，且在重度苯丙酮尿症中无明确的有效性证据。
