当前的德国新生儿筛查(NBS)小组包括13种遗传代谢疾病(IMD)。此外,NBS在德国西南部的一项试点研究确定了患有丙酸血症(PA)的个体,甲基丙二酸血症(MMA),合并和分离的再甲基化障碍(例如,钴胺素[cbl]C和亚甲基四氢叶酸还原酶[MTHFR]缺乏症),胱硫醚β-合酶(CBS)缺乏症,和新生儿cbl缺乏通过一个多层算法。在多中心观察研究中评估了筛查个体的长期健康益处。27名患有IMD的筛查个体(PA[N=13],MMA[N=6],cblC缺乏[N=5],MTHFR缺乏[N=2]和CBS缺乏[N=1]),42例新生儿cbl缺乏症患者的中位随访时间为3.6年.17名接受筛查的IMD患者(63%)至少经历过一次代谢代偿,其中14人是新生儿,6人甚至在国家统计局报告之前(PA,cbl无反应MMA)。尽管NBS和立即治疗,三名PA患者仍死亡。15例(79%)PA或MMA患者和所有cblC缺乏症患者发展为永久性的,主要是神经症状,而患有MTHFR的人,CBS,新生儿cbl缺乏具有良好的临床结局。利用组合的多层算法,我们证明,NBS和专门的代谢护理对MTHFR缺乏的个体产生了实质性的益处,CBS缺乏,新生儿cbl缺乏症,在某种程度上,cbl反应性MMA和cblC缺乏症。然而,对于PA和cbl无反应性MMA的个体,其优势不太明显。简介:通过新生儿筛查和随后的专门代谢护理进行早期检测,可改善MTHFR缺乏症和胱硫醚-β合酶缺乏症患者的临床结局和生存率。并且在某种程度上在钴胺素反应性甲基丙二酸血症(MMA)和cblC缺乏症中,而由于高(新生儿)失代偿率,对丙酸血症和钴胺素无反应性MMA的个体的益处不太明显,死亡率,和长期并发症。
The current German newborn screening (NBS) panel includes 13 inherited metabolic diseases (IMDs). In addition, a NBS pilot study in Southwest Germany identifies individuals with propionic acidemia (PA), methylmalonic acidemia (MMA), combined and isolated remethylation disorders (e.g., cobalamin [cbl] C and methylenetetrahydrofolate reductase [MTHFR] deficiency), cystathionine β-synthase (CBS) deficiency, and neonatal cbl deficiency through one multiple-tier algorithm. The long-term health benefits of screened individuals are evaluated in a multicenter observational study. Twenty seven screened individuals with IMDs (PA [N = 13], MMA [N = 6], cblC deficiency [N = 5], MTHFR deficiency [N = 2] and CBS deficiency [N = 1]), and 42 with neonatal cbl deficiency were followed for a median of 3.6 years. Seventeen screened IMD patients (63%) experienced at least one metabolic decompensation, 14 of them neonatally and six even before the NBS report (PA, cbl-nonresponsive MMA). Three PA patients died despite NBS and immediate treatment. Fifteen individuals (79%) with PA or MMA and all with cblC deficiency developed permanent, mostly neurological symptoms, while individuals with MTHFR, CBS, and neonatal cbl deficiency had a favorable clinical outcome. Utilizing a combined multiple-tier algorithm, we demonstrate that NBS and specialized metabolic care result in substantial benefits for individuals with MTHFR deficiency, CBS deficiency, neonatal cbl deficiency, and to some extent, cbl-responsive MMA and cblC deficiency. However, its advantage is less evident for individuals with PA and cbl-nonresponsive MMA. SYNOPSIS: Early detection through newborn screening and subsequent specialized metabolic care improve clinical outcomes and survival in individuals with MTHFR deficiency and cystathionine-β-synthase deficiency, and to some extent in cobalamin-responsive methylmalonic acidemia (MMA) and cblC deficiency while the benefit for individuals with propionic acidemia and cobalamin-nonresponsive MMA is less evident due to the high (neonatal) decompensation rate, mortality, and long-term complications.