肠内营养粉剂AA-PKU2治疗1~8岁苯丙酮尿症患儿的有效性和安全性研究

Efficacy and safety of a phenylalanine-free amino acid-based enteral formula (AA-PKU2) in 1-8 year-old children with phenylketonuria：a prospective, open, self-controlled and multi-center study in China

摘要:

目的 评价肠内营养粉剂AA-PKU2对1~8岁苯丙酮尿症（PKU）患儿治疗的有效性和安全性。方法 2009年7月至2011年5月采用前瞻、开放、自身前后对照、多中心临床研究方法，共入组1岁至7岁4个月PKU患儿121例，评估肠内营养粉剂AA-PKU2治疗前、治疗8周及32周后患儿血苯丙氨酸（PHE）浓度、智能发育（1~4岁Gesell法，>4岁WPPSI或WISR-R法）、身高、体重、头围、血常规、尿常规、肝肾功能、血脂和蛋白水平等血清营养学指标的变化以及不良事件发生情况。结果 AA-PKU2治疗8周和32周后患儿血PHE浓度平均水平分别为353±253、361±280 μmol/L，与治疗前 （487±327 μmol/L）相比，差异有统计学意义（P<0.01）；治疗8周和32周后血PHE浓度≤360 μmol/L的控制率分别为65.5%、66.7%。在Gesell法评估的患儿中，AA-PKU2治疗8周和32周后总发育商与治疗前比较差异无统计学意义，但显示了智能改善的趋势；在WPPSI或WISR-R法评估的患儿中，AA-PKU2治疗8周和32周后总智商比治疗前明显增加（P<0.01）。AA-PKU2治疗8周和32周后患儿的身高、体重、头围与治疗前比较均显著增加（P<0.01），与同年龄段正常儿童的指标相当。治疗8周和32周后患儿血浆总蛋白、白蛋白、前白蛋白、总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白平均水平与治疗前的平均水平基本相当，均在正常范围内。与AA-PKU2治疗相关的不良事件发生率为2.5%（3例），均为轻度腹泻，未特殊处理而好转。结论 肠内营养粉剂AA-PKU2能有效控制1~8岁患儿的血PHE浓度在360 μmol/L以内；通过有效控制患儿血PHE浓度，可改善患儿的智力发育，满足患儿正常生长发育的需要，且临床应用安全、耐受性好。

Abstract:

Objective To evaluate the efficacy and safety of a phenylalanine-free amino acid-based enteral formula (AA-PKU2) in the treatment of children with phenylketonuria (PKU) aged 1-8 years. Methods A prospective, open, self-controlled, multi-center trial was performed, enrolling 121 PKU children (1-8 years in age) consecutively between July, 2009 and May, 2011. Enteral nutrition therapy was administered for 32 weeks. The data on blood phenylalanine (PHE) levels, metal development, weight, height, head circumference, serum nutritional biomarkers (total protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), and measurements from routine blood and urine examinations and from renal and hepatic function tests were collected before the therapy and at 8 weeks and 32 weeks after the therapy and were comparatively analyzed. Results The mean blood PHE level at 8 and 32 weeks of AA-PKU2 treatment was 353±253 and 361±280 μmol/L respectively, significantly lower than that before the treatment (487±327 μmol/L; P<0.01). The difference in intelligence quotient scores before and after AA-PKU2 treatment was not significant (P >0.05) when assessed by the Gesell tests in children aged 1-4 years but significant (P<0.01) when assessed by WPPSI or WISR-R tests in children over 4 years. The average height, weight and head circumference at 8 and 32 weeks after treatment were significantly increased as compared to these measurements before treatment (P<0.01) with absolute levels similar to those in the control children. In contrast, the mean values of total protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol at both time points were not different either from those prior to the treatment or from those in the control children. Mild diarrhea was the adverse events associated with AA-PKU2 treatment, which occurred in 3 (2.5%) cases. All these 3 patients fully recovered without treatment. Conclusions The phenylalanine-free amino acid-based formula, AA-PKU2, is effective and safe in controlling blood PHE levels and improving mental development with adequate nutritional support in PKU.