Division of Child Neurology and Metabolic Medicine, Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Department for Inborn Metabolic Diseases, University Children's Hospital, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Nutrients. 2023 Jul 28;15(15):3355. doi: 10.3390/nu15153355.
Newborn screening (NBS) programs are effective measures of secondary prevention and have been successively extended. We aimed to evaluate NBS for methylmalonic acidurias, propionic acidemia, homocystinuria, remethylation disorders and neonatal vitamin B deficiency, and report on the identification of cofactor-responsive disease variants. This evaluation of the previously established combined multiple-tier NBS algorithm is part of the prospective pilot study "NGS2025" from August 2016 to September 2022. In 548,707 newborns, the combined algorithm was applied and led to positive NBS results in 458 of them. Overall, 166 newborns (prevalence 1: 3305) were confirmed (positive predictive value: 0.36); specifically, methylmalonic acidurias (N = 5), propionic acidemia (N = 4), remethylation disorders (N = 4), cystathionine beta-synthase (CBS) deficiency (N = 1) and neonatal vitamin B deficiency (N = 153). The majority of the identified newborns were asymptomatic at the time of the first NBS report (total: 161/166, inherited metabolic diseases: 9/14, vitamin B deficiency: 153/153). Three individuals were cofactor-responsive (methylmalonic acidurias: 2, CBS deficiency: 1), and could be treated by vitamin B, vitamin B respectively, only. In conclusion, the combined NBS algorithm is technically feasible, allows the identification of attenuated and severe disease courses and can be considered to be evaluated for inclusion in national NBS panels.
新生儿筛查（NBS）计划是二级预防的有效措施，已相继得到扩展。我们旨在评估甲基丙二酸血症、丙酸血症、高同型半胱氨酸血症、再甲基化障碍和新生儿维生素 B 缺乏症的 NBS，并报告辅助因子反应性疾病变异体的鉴定。这项对先前建立的联合多层面 NBS 算法的评估是 2016 年 8 月至 2022 年 9 月前瞻性试点研究“NGS2025”的一部分。在 548,707 名新生儿中，应用联合算法导致其中 458 名出现阳性 NBS 结果。总体而言，有 166 名新生儿（患病率 1:3305）得到确诊（阳性预测值：0.36）；具体而言，甲基丙二酸血症（N=5）、丙酸血症（N=4）、再甲基化障碍（N=4）、胱硫醚β-合酶（CBS）缺乏症（N=1）和新生儿维生素 B 缺乏症（N=153）。在首次 NBS 报告时，大多数确诊的新生儿无症状（总计：161/166，遗传性代谢疾病：9/14，维生素 B 缺乏症：153/153）。有 3 名个体为辅助因子反应性（甲基丙二酸血症：2 名，CBS 缺乏症：1 名），仅分别用维生素 B、维生素 B 治疗即可。总之，联合 NBS 算法在技术上是可行的，允许识别轻度和重度疾病过程，可考虑评估纳入国家 NBS 计划。
