Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5 years experience
Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5 years experience
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DOI：
10.1007/s10545-011-9300-1
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发表时间：
2011-06-01
影响因子：
4.2
通讯作者：
Blau, Nenad
中科院分区：
文献类型：
--
作者：
Opladen, Thomas;Abu Seda, Bettina;Blau, Nenad
即使是轻度高苯丙氨酸血症（HPA）的新生儿，也需要尽快排除四氢生物蝶呤（BH 4）缺乏症。鉴别诊断最常通过分析尿新蝶呤和生物蝶呤进行。2005年提出了一种新的滤纸干血斑（DBS）中新蝶呤、生物蝶呤和其他蝶呤的测定方法。为了评估这种方法作为HPAs鉴别诊断的标准工具的有用性，我们分析了5年内362例HPA患者DBS中的新蝶呤、生物蝶呤、蝶呤和二氢蝶啶还原酶活性。为HPA人群建立了依赖性的参考值。64例BH 4缺乏症患者（27例6-异戊酰-四氢蝶呤合酶缺乏症，7例GTP环化水解酶I缺乏症，30例二氢蝶啶还原酶）被确定。计算每种变体的DBS中新蝶呤和生物蝶呤的参考值。6-异戊酰-四氢蝶呤合酶和GTP环化水解酶I缺乏症可以单独通过新蝶呤和生物蝶呤分析来诊断，而对于二氢蝶啶还原酶缺乏症的诊断，来自相同DBS的酶活性的额外测定是必需的。关于测试灵敏度，每血红蛋白的新蝶呤和生物蝶呤浓度的解释比每升新蝶呤和生物蝶呤的解释更有效。应始终计算生物蝶呤占新蝶呤和生物蝶呤总和的百分比。此外，血红蛋白浓度的测定是有效提取新蝶呤和生物蝶呤的重要措施。虽然尿液中新蝶呤和生物蝶呤的测量由于浓度较高而更敏感，但我们的数据证明了DBS测量对BH 4缺乏症的常规诊断的有用性。
In every newborn with even mild hyperphenylalaninemia (HPA) tetrahydrobiopterin (BH4) deficiencies need to be excluded as soon as possible. Differential diagnosis is most commonly performed by analysis of urinary neopterin and biopterin. In 2005 a new method for the measurement of neopterin, biopterin and other pterins in dried blood spot (DBS) on filter paper was introduced. In order to evaluate the usefulness of this method as a standard tool for differential diagnosis of HPAs we analyzed neopterin, biopterin, pterin and dihydropteridine reductase activity in DBS from 362 patients with HPA over the period of five years. Age-dependent reference values were established for the HPA population. Sixty-four patients with BH4 deficiency (27 patients with 6-pyruvoyl-tetrahydropterin synthase deficiency, seven with GTP cyclohydrolase I deficiency, and 30 with dihydropteridine reductase) were identified. Reference values for neopterin and biopterin in DBS were calculated for each of the variants. 6-pyruvoyl-tetrahydropterin synthase and GTP cyclohydrolase I deficiency can be diagnosed by neopterin and biopterin analysis alone, while for diagnosis of dihydropteridine reductase deficiency additional determination of enzyme activity from the same DBS is essential. Regarding test sensitivity, the interpretation of neopterin and biopterin concentration per hemoglobin is more valid than the interpretation of neopterin and biopterin per liter. Percentage of biopterin, of the sum of neopterin and biopterin should always be calculated. In addition, determination of hemoglobin concentration is essential as a measure for efficient extraction of neopterin and biopterin. Although the measurement of neopterin and biopterin in urine is more sensitive due to the higher concentrations present, our data prove the usefulness of their measurement from DBS for the routine diagnosis of BH4 deficiencies.