In vivo studies of phenylalanine hydroxylase by phenylalanine breath test:: Diagnosis of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency
In vivo studies of phenylalanine hydroxylase by phenylalanine breath test:: Diagnosis of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency
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DOI：
10.1203/01.pdr.0000141520.06524.51
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发表时间：
2004-11-01
影响因子：
3.6
通讯作者：
Yamano, T
中科院分区：
文献类型：
--
作者：
Okano, Y;Hase, Y;Yamano, T
四氢生物蝶呤（BH4）-反应性苯丙氨酸羟化酶（PAH）缺乏症的特征是BH4负荷试验后血液苯丙氨酸水平降低。大多数BH4反应性PAH缺乏症病例包括轻度苯丙酮尿症（PKU）或轻度高苯丙氨酸血症（HPA），但并非所有轻度PKU患者均对BH4有反应。我们进行了苯丙氨酸呼气试验作为可靠的方法来确定BH4的反应性。苯丙氨酸呼气试验定量测量L-[1-C-13]苯丙氨酸转化为（CO2）-C-13，是一种无创和快速的测试。20名日本HPA患者接受了10 mg/kg C-13-苯丙氨酸（10 mg/kg）联合或不联合10 mg（.）kg（-1）（.）d（-1）的BH_4处理3d。苯丙氨酸呼气试验[累积恢复率（CRR）]可以区分对照受试者（15.4 +/-1.5%）、杂合子（10.3 +/-1.0%）、轻度HPA（2.74%）、轻度PKU（1.13 +/-0.14%）和经典PKU患者（0.29 +/-0.14%）。轻度PKU患者的基因型为轻度（L52S、R241C、R408Q）和重度突变的复合杂合子，而轻度HPA患者为R241C纯合子。CRR与治疗前苯丙氨酸水平呈负相关，表明基因剂量对PKU的影响。BH4负荷使轻度PKU的CRR从1.13 +/-0.14增加到2.95 +/-1.14%（2.6倍），轻度HPA的CRR从2.74增加到7.22%（2.6倍）。5 - 6%的CRR反映维持适当的血清苯丙氨酸水平。苯丙氨酸呼气试验可用于诊断BH4反应性PAH缺乏症，并确定BH4的最佳剂量，而不会增加血液苯丙氨酸水平。
Tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase (PAH) deficiency is characterized by reduction of blood phenylalanine level after a BH4-loading test. Most cases of BH4-responsive PAH deficiency include mild phenylketonuria (PKU) or mild hyperphenylalaninemia (HPA), but not all patients with mild PKU respond to BH4. We performed the phenylalanine breath test as reliable method to determine the BH4 responsiveness. Phenylalanine breath test quantitatively measures the conversion of L-[1-C-13] phenylalanine to (CO2)-C-13 and is a noninvasive and rapid test. Twenty Japanese patients with HPA were examined with a dose of 10 mg/kg of C-13-phenylalanine with or without a dose of 10 mg (.) kg(-1) (.) d(-1) of BH4 for 3 d. The phenylalanine breath test [cumulative recovery rate (CRR)] could distinguish control subjects (15.4 +/- 1.5%); heterozygotes (10.3 +/- 1.0%); and mild HPA (2.74%), mild PKU (1.13 +/- 0.14%), and classical PKU patients (0.29 +/- 0.14%). The genotypes in mild PKU cases were compound heterozygotes with mild (L52S, R241C, R408Q) and severe mutations, whereas a mild HPA case was homozygote of R241C. CRR correlated inversely with pretreatment phenylalanine levels, indicating the gene dosage effects on PKU. BH4 loading increased CRR from 1.13 +/- 0.14 to 2.95 +/- 1.14% (2.6-fold) in mild PKU and from 2.74 to 7.22% (2.6-fold) in mild HPA. A CRR of 5 to 6% reflected maintenance of appropriate serum phenylalanine level. The phenylalanine breath test is useful for the diagnosis of BH4-responsive PAH deficiency and determination of the optimal dosage of BH4 without increasing blood phenylalanine level.