Schroder Theresa H, Mattman Andre, Sinclair Graham, Vallance Hilary D, Lamers Yvonne
Food, Nutrition and Health, Faculty of Land and Food Systems, The University of British Columbia, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada; Child and Family Research Institute, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada.
Child and Family Research Institute, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada; Department of Clinical Chemistry and Laboratory Medicine, The University of British Columbia; St Paul's Hospital, 1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada.
Clin Biochem. 2016 Sep;49(13-14):973-8. doi: 10.1016/j.clinbiochem.2016.03.007. Epub 2016 Apr 15.
Unrecognized vitamin B12 (B-12) deficiency in early infancy can lead to poor development of the child. Methylmalonic acid (MMA) is the most specific functional biomarker of B-12 status. To facilitate timely diagnosis and treatment of neonatal B-12 deficiency, the objective of this study was to calculate a reference interval of MMA in dried blood spots (DBSs) of healthy, term newborns.
MMA was quantified in 160 newborn DBSs, routinely collected for newborn screening, using LC-MS/MS. The reference interval of DBS MMA was calculated according to current guidelines (CLSI EP28-A3c). The effect of storage at room temperature on DBS MMA concentrations was determined.
The mean DBS MMA concentration of 160 healthy, term newborns was 16.8pmol (95% CI: 15.9-17.6pmol)/8-mm spot. The reference interval (2.5th to 97.5th percentile) for MMA was 9.89 to 29.3pmol/8-mm spot (0.450 to 1.33μmol/L whole blood). DBS MMA concentrations correlated positively (p<0.005) with storage time at room temperature. DBS MMA concentrations of children with methylmalonic acidemia (n=4) were above the upper limit of the reference interval.
This is the first study to present a reference interval for DBS MMA of healthy, term newborns utilizing a new highly sensitive MMA method. Analysis of DBS MMA collected during newborn screening may have the potential to identify newborns with acquired B-12 deficiency. Newborn DBS MMA concentrations increase with storage at room temperature, therefore, sample storage has to be monitored for evaluation of DBS MMA data.
婴儿早期未被识别的维生素B12（B - 12）缺乏会导致儿童发育不良。甲基丙二酸（MMA）是B - 12状态最具特异性的功能生物标志物。为便于及时诊断和治疗新生儿B - 12缺乏，本研究的目的是计算健康足月儿干血斑（DBS）中MMA的参考区间。
使用液相色谱 - 串联质谱法（LC - MS/MS）对160份用于新生儿筛查的新生儿DBS进行MMA定量分析。根据现行指南（CLSI EP28 - A3c）计算DBS中MMA的参考区间。确定室温储存对DBS中MMA浓度的影响。
160名健康足月儿的DBS中MMA平均浓度为16.8pmol（95%CI：15.9 - 17.6pmol）/8mm血斑。MMA的参考区间（第2.5百分位数至第97.5百分位数）为9.89至29.3pmol/8mm血斑（全血0.450至1.33μmol/L）。DBS中MMA浓度与室温下的储存时间呈正相关（p<0.005）。甲基丙二酸血症患儿（n = 4）的DBS中MMA浓度高于参考区间上限。
这是第一项利用新的高灵敏度MMA方法给出健康足月儿DBS中MMA参考区间的研究。对新生儿筛查期间收集的DBS中MMA进行分析可能有助于识别获得性B - 12缺乏的新生儿。新生儿DBS中MMA浓度随室温储存而增加，因此，在评估DBS中MMA数据时必须监测样本储存情况。
