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Abstract：
Alteration of vitamin B12 metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B12 deficiency have been detected by clinical symptoms and only few of them trough NBS programs. We aim to assess the usefulness of the second-tier test: methylmalonic acid (MMA), methylcitric acid (MCA) and homocysteine (Hcys) in our newborn screening program and explore the implications on the detection of cobalamin (vitamin B12) related disorders, both genetic and acquired conditions.
A screening strategy using the usual primary markers followed by the analysis of MMA, MCA and Hcys as second tier-test in the first dried blood spot (DBS) was developed and evaluated.
During the period 2015-2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B12 deficiency (incidence 1:1989), 19 with genetic disorders (incidence 1:13,613) and 13 were false positive. No false negatives were notified. Concerning the second-tier test, the percentage of cases with MMA above the cut-off levels, both for genetic and acquired conditions was very similar (58% and 60%, respectively). Interestingly, the percentage of cases with increased levels of Hcys was higher in acquired conditions than in genetic disorders (87% and 47%, respectively). In contrast, MCA was high only in 5% of the acquired conditions versus in 53% of the genetic disorders, and it was always very high in all patients with propionic acidemia.
When screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B12 deficiency should be done. The results of our strategy support the inclusion of this acquired condition in the NBS programs, as it is easily detectable and allows the adoption of corrective measures to avoid the consequences of its deficiency.
A screening strategy using the usual primary markers followed by the analysis of MMA, MCA and Hcys as second tier-test in the first dried blood spot (DBS) was developed and evaluated.
During the period 2015-2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B12 deficiency (incidence 1:1989), 19 with genetic disorders (incidence 1:13,613) and 13 were false positive. No false negatives were notified. Concerning the second-tier test, the percentage of cases with MMA above the cut-off levels, both for genetic and acquired conditions was very similar (58% and 60%, respectively). Interestingly, the percentage of cases with increased levels of Hcys was higher in acquired conditions than in genetic disorders (87% and 47%, respectively). In contrast, MCA was high only in 5% of the acquired conditions versus in 53% of the genetic disorders, and it was always very high in all patients with propionic acidemia.
When screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B12 deficiency should be done. The results of our strategy support the inclusion of this acquired condition in the NBS programs, as it is easily detectable and allows the adoption of corrective measures to avoid the consequences of its deficiency.
摘要：
维生素B12代谢的改变可以是遗传的或获得性的，会导致贫血，未能茁壮成长，发育退化，甚至不可逆的神经损伤。因此,早期诊断和干预至关重要。大多数获得性维生素B12缺乏症的新生儿病例都是通过临床症状发现的，只有少数通过NBS计划。我们的目的是评估第二层测试的有用性：甲基丙二酸（MMA），我们的新生儿筛查计划中的甲基柠檬酸（MCA）和同型半胱氨酸（Hcys），并探讨对钴胺（维生素B12）相关疾病的检测的意义，遗传和后天条件。
使用通常的主要标记然后分析MMA的筛选策略，开发并评估了MCA和Hcys作为第一干血斑（DBS）中的第二层测试。
在2015-2018年期间，共筛查了258,637名新生儿，导致130名新生儿患有获得性维生素B12缺乏症（发病率1：1989）。19例遗传性疾病（发生率1：13,613）和13例假阳性。没有漏报。关于第二层测试，MMA高于截止水平的病例百分比，遗传条件和后天条件都非常相似(58%和60%，分别)。有趣的是,在获得性疾病中，Hcys水平升高的病例百分比高于遗传性疾病（87％和47％，分别)。相比之下,MCA仅在5％的获得性疾病中高于53％的遗传性疾病，在所有丙酸血症患者中，它总是非常高。
在筛查甲基丙二酸血症和高半胱氨酸尿症时，应与获得性维生素B12缺乏症进行鉴别诊断。我们的战略结果支持将这种后天条件纳入国家统计局计划，因为它很容易被发现，并允许采取纠正措施，以避免其缺陷的后果。
使用通常的主要标记然后分析MMA的筛选策略，开发并评估了MCA和Hcys作为第一干血斑（DBS）中的第二层测试。
在2015-2018年期间，共筛查了258,637名新生儿，导致130名新生儿患有获得性维生素B12缺乏症（发病率1：1989）。19例遗传性疾病（发生率1：13,613）和13例假阳性。没有漏报。关于第二层测试，MMA高于截止水平的病例百分比，遗传条件和后天条件都非常相似(58%和60%，分别)。有趣的是,在获得性疾病中，Hcys水平升高的病例百分比高于遗传性疾病（87％和47％，分别)。相比之下,MCA仅在5％的获得性疾病中高于53％的遗传性疾病，在所有丙酸血症患者中，它总是非常高。
在筛查甲基丙二酸血症和高半胱氨酸尿症时，应与获得性维生素B12缺乏症进行鉴别诊断。我们的战略结果支持将这种后天条件纳入国家统计局计划，因为它很容易被发现，并允许采取纠正措施，以避免其缺陷的后果。
