Newborn Population Screening for Classic Homocystinuria by Determination of Total Homocysteine from Guthrie Cards
Newborn Population Screening for Classic Homocystinuria by Determination of Total Homocysteine from Guthrie Cards
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DOI：
10.1016/j.jpeds.2009.09.054
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发表时间：
2010-03-01
影响因子：
5.1
通讯作者：
Hoffmann, Georg F.
中科院分区：
文献类型：
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作者：
Gan-Schreier, Hongying;Kebbewar, Moustafa;Hoffmann, Georg F.
目的通过新生儿筛查早期识别胱硫醚β-合酶。研究设计采用新型、稳健的高效液相色谱串联质谱法测定干燥血斑中的总同型半胱氨酸。同型半胱氨酸的定量在高达 50 μmol/L 的工作范围内呈线性。为了进行突变分析，对 DNA 进行了卡塔尔常见的 2 种突变测试。结果 两种方法均被证明适合高通量处理。两年内，12 603 名卡塔尔本土婴儿中发现 7 名患有典型同型半胱氨酸尿症，发病率为 1:1800。分子筛查可能会漏掉 1 名纯合子患者，因为该患者之前未在卡塔尔人群中发现过突变。在 3 年的时间里，通过对卡塔尔出生的所有新生儿（n = 46 406）的同型半胱氨酸筛查，总共发现了 14 例经典同型半胱氨酸尿症病例。同型半胱氨酸始终升高，而蛋氨酸仅在 7 例中升高。结论 该研究为新生儿筛查胱硫醚 β-合酶缺乏症提供了一种可靠的方法，即使在出生后 3 天内采集样本，灵敏度也高达 100%。 (J Pediatr 2010；156：42732)。
Objective To allow early recognition of cystathionine beta-synthase by newborn screening.Study design Total homocysteine was determined in dried blood spots with a novel, robust high-performance liquid chromatography method with tandem mass spectrometry. Quantification of homocysteine was linear over a working range up to 50 mu mol/L. For mutation analysis, DNA was tested for 2 mutations common in Qatar.Results Both methods proved to be suitable for high throughput processing. In 2 years, 7 infants with classic homocystinuria were identified of 12 603 native Qatari infants, yielding an incidence of 1:1800. Molecular screening would have missed 1 patient homozygous for a mutation not previously identified in the Qatari population. Over a period of 3 years, a total of 14 cases of classic homocystinuria were detected by screening of homocysteine from all newborn infants born in Qatar (n = 46 406). Homocysteine was always elevated, whereas methionine was elevated in only 7 cases.Conclusions The study offers a reliable method for newborn screening for cystathionine beta-synthase deficiency, reaching a sensitivity of up to 100%, even if samples are taken within the first 3 days of life. (J Pediatr 2010; 156: 42732).