Tangeraas Trine, Ljungblad Ulf W, Lutvica Elma, Kristensen Erle, Rowe Alex D, Bjørke-Monsen Anne-Lise, Rootwelt-Revheim Terje, Sæves Ingjerd, Pettersen Rolf D
Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, 0424 Oslo, Norway.
European Reference Network for Hereditary Metabolic Disorders (MetabERN), 0424 Oslo, Norway.
Int J Neonatal Screen. 2023 Jan 5;9(1):3. doi: 10.3390/ijns9010003.
Untreated vitamin B12 (B12) deficiency may cause delayed development in infants. Several newborn screening (NBS) programs have reported an increased detection rate of B12 deficiency when second-tier dried blood spot (DBS) analyses of total homocysteine (tHcy) and methylmalonic acid (MMA) are included. This is a retrospective study of newborns reported from NBS during 2012−2021 with confirmed B12 deficiency. DBSs were retrieved from the NBS biobank for second-tier MMA and tHcy analysis. Thirty-one newborns were diagnosed with B12 deficiency out of 552970 screened. Twenty-five were ascertained from sixty-one false positive (FP) cases of methylmalonic acidemia and propionic acidemia (PA), and six infants screened positive for other NBS metabolic diseases with propionylcarnitine (C3) in the normal range. In the original DBS, 7/23 (30%) and 12/23 (52%) of B12-deficient newborns with FP methylmalonic acidemia/PA had MMA and tHcy > 99th percentile. B12 deficiency was a common differential diagnosis of screening positive for methylmalonic and PA. C3 failed to identify a subset of newborns with B12 deficiency. Second-tier MMA and tHcy analyses in the DBS showed suboptimal sensitivity for identifying infants with B12 deficiency. The shortcomings of NBS should be acknowledged when considering B12 deficiency as a primary target of NBS panels.
未经治疗的维生素B12（B12）缺乏可能导致婴儿发育迟缓。多项新生儿筛查（NBS）项目报告称，当纳入同型半胱氨酸（tHcy）和甲基丙二酸（MMA）的二级干血斑（DBS）分析时，B12缺乏的检出率会增加。这是一项对2012年至2021年期间NBS报告的确诊B12缺乏新生儿的回顾性研究。从NBS生物样本库中检索DBS样本，用于二级MMA和tHcy分析。在552970例筛查新生儿中，有31例被诊断为B12缺乏。其中25例是从61例假阳性（FP）甲基丙二酸血症和丙酸血症（PA）病例中确诊的，另外6例筛查出其他NBS代谢疾病阳性且丙酰肉碱（C3）在正常范围内的婴儿。在最初的DBS样本中，伴有FP甲基丙二酸血症/PA的B12缺乏新生儿中，7/23（30%）和12/23（52%）的MMA和tHcy高于第99百分位数。B12缺乏是甲基丙二酸血症和PA筛查阳性的常见鉴别诊断。C3未能识别出一部分B12缺乏的新生儿。DBS中的二级MMA和tHcy分析在识别B12缺乏婴儿方面显示出敏感性欠佳。在将B12缺乏作为NBS筛查指标的主要目标时，应认识到NBS存在的不足。
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