Department of Human Genetics, Emory University School of Medicine, Decatur, GA 30033, USA.
Mol Genet Metab. 2011 Dec;104(4):485-91. doi: 10.1016/j.ymgme.2011.09.009. Epub 2011 Sep 16.
Tetrahydrobiopterin (BH(4)) responsiveness is currently defined as a decrease in plasma phenylalanine concentrations in patients with phenylketonuria (PKU). This definition does not offer insight beyond the initial assessment of patients, which may lead to treatment ambiguity in patients who only experience an initial decrease in plasma phenylalanine concentrations. We present our experience with a novel classification approach using sequentially-applied criteria. Plasma phenylalanine concentrations were measured at baseline and after one month of BH(4) therapy (20 mg/kg/day) in 58 PKU patients (34 M, 24 F; age 17.3±11.0 years). Thirty-two patients (55.2%) were classified as "preliminary responders" at one month, experiencing at least a 15% decrease in plasma phenylalanine concentrations. Preliminary responders' ability to liberalize their dietary restrictions was then systematically assessed. "Definitive responders" were defined as preliminary responders who could increase their dietary phenylalanine tolerance by at least 300 mg/day and lower prescribed medical food needs by at least 25% while maintaining metabolic control (plasma phenylalanine ≤360 μmol/L) and consuming adequate dietary protein. Preliminary responders who could not liberalize their diets according to these criteria were classified as "provisional responders." Nineteen patients (32.8% of patients initiating BH(4) therapy) met the definitive responder criteria, increasing dietary phenylalanine tolerance from 704±518 mg/day to 1922±612 mg/day and reducing medical food to 16.7±19.5% of their baseline prescription. Nine patients (15.5% of patients initiating BH(4) therapy) were classified as provisional responders, all remaining on 100% of their baseline medical food prescription. From this classification approach, a subgroup of provisionally responsive patients emerged who experienced an initial decrease in plasma phenylalanine concentrations but who could not substantially increase their dietary phenylalanine tolerance or decrease medical food needs. Diet liberalization is an essential component of BH(4)-responsiveness classification.
四氢生物蝶呤（BH4）反应性目前定义为苯丙酮尿症（PKU）患者血浆苯丙氨酸浓度降低。该定义除了对患者进行初步评估外，没有提供其他见解，这可能导致仅经历血浆苯丙氨酸浓度初始降低的患者的治疗模糊。我们提出了一种使用逐步应用标准的新分类方法的经验。在 58 例 PKU 患者（34 例男性，24 例女性；年龄 17.3±11.0 岁）中，测量了基线和 BH4 治疗一个月（20mg/kg/天）后的血浆苯丙氨酸浓度。32 例患者（55.2%）在一个月时被归类为“初步反应者”，血浆苯丙氨酸浓度至少降低了 15%。然后系统评估了“初步反应者”放宽饮食限制的能力。“明确反应者”被定义为能够将饮食苯丙氨酸耐受性至少增加 300mg/天并将规定的特殊医学用途食品需求降低至少 25%，同时保持代谢控制（血浆苯丙氨酸≤360μmol/L）并摄入足够的饮食蛋白质的初步反应者。根据这些标准无法放宽饮食的初步反应者被归类为“临时反应者”。19 例患者（开始 BH4 治疗的患者的 32.8%）符合明确反应者标准，将饮食苯丙氨酸耐受性从 704±518mg/天增加到 1922±612mg/天，并将特殊医学用途食品减少到基线处方的 16.7±19.5%。9 例患者（开始 BH4 治疗的患者的 15.5%）被归类为临时反应者，他们都继续服用 100%的基线特殊医学用途食品处方。从这种分类方法中，出现了一组临时反应者，他们最初血浆苯丙氨酸浓度降低，但不能大幅增加饮食苯丙氨酸耐受性或减少特殊医学用途食品需求。饮食放宽是 BH4 反应性分类的一个重要组成部分。
