Gramer Gwendolyn, Abdoh Ghassan, Ben-Omran Tawfeg, Shahbeck Noora, Ali Rehab, Mahmoud Laila, Fang-Hoffmann Junmin, Hoffmann Georg F, Al Rifai Hilal, Okun Jürgen G
University of Heidelberg, Center for Pediatric and Adolescent Medicine, Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.
World J Pediatr. 2017 Apr;13(2):136-143. doi: 10.1007/s12519-017-0003-z. Epub 2017 Jan 15.
Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-ß-synthase deficiency). Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar.
A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine, methionine-phenylalanine-ratio and propionylcarnitine as second-tiers. Proposed cut-offs were also retrospectively evaluated in newborn screening samples of 12 patients with remethylation disorders and vitamin B deficiency from Qatar and Germany.
Over a 12 months period, the proposed strategy led to a decrease in the recall rate in homocysteine screening for Qatar from 1.09% to 0.68%, while allowing for additional systematic inclusion of remethylation disorders and vitamin B deficiency into the screening panel for Qatar. In the evaluated period the applied strategy would have detected all patients with classical homocystinuria identified by the previous strategy and in addition 5 children with maternal nutritional vitamin B deficiency and one patient with an isolated remethylation disorder. Additional retrospective evaluation of newborn screening samples of 12 patients from Germany and Qatar with remethlyation disorders or vitamin B deficiency showed that all of these patients would have been detected by the cut-offs used in the proposed new strategy. In addition, an adapted strategy for Germany using methionine, methionine-phenylalanine-ratio and propionylcarnitine as first-tier, and homocysteine as a second-tier test was also positively evaluated retrospectively.
The proposed strategy for samples from Qatar allows inclusion of remethylation disorders and vitamin B deficiency in the screening panel, while lowering the recall rate. An adapted second-tier strategy is presented for screening in Germany and will be prospectively evaluated over the next years in a pilot project named "Newborn Screening 2020".
新生儿筛查是甲基化障碍和经典型同型胱氨酸尿症（胱硫醚-β-合酶缺乏症）早期诊断及成功治疗的前提条件。多年来，在卡塔尔，利用干血斑中总同型半胱氨酸测量进行经典型同型胱氨酸尿症的新生儿筛查一直非常成功。
针对卡塔尔新生儿，制定并评估了一种用于甲基化障碍和同型胱氨酸尿症的优化新生儿筛查策略，该策略以总同型半胱氨酸测量作为一级检测指标，以甲硫氨酸、甲硫氨酸-苯丙氨酸比值和丙酰肉碱作为二级检测指标。还对卡塔尔和德国12例甲基化障碍及维生素B缺乏症患者的新生儿筛查样本进行回顾性评估，以确定所提议的临界值。
在12个月的时间里，所提议的策略使卡塔尔同型半胱氨酸筛查的召回率从1.09%降至0.68%，同时能将甲基化障碍和维生素B缺乏症系统性地纳入卡塔尔的筛查项目。在评估期间，所应用的策略能够检测出先前策略所识别出的所有经典型同型胱氨酸尿症患者，此外还能检测出5例因母亲营养性维生素B缺乏的儿童以及1例孤立性甲基化障碍患者。对卡塔尔和德国12例甲基化障碍或维生素B缺乏症患者的新生儿筛查样本进行的额外回顾性评估表明，所提议的新策略所使用的临界值能够检测出所有这些患者。此外，一种适用于德国的策略，即以甲硫氨酸、甲硫氨酸-苯丙氨酸比值和丙酰肉碱作为一级检测指标，以同型半胱氨酸作为二级检测指标，经回顾性评估也得到了积极评价。
所提议的针对卡塔尔样本的策略能够将甲基化障碍和维生素B缺乏症纳入筛查项目，同时降低召回率。本文还提出了一种适用于德国的二级筛查策略，并将在名为“2020新生儿筛查”的试点项目中在未来几年进行前瞻性评估。
