Ficicioglu Can, Ahrens-Nicklas Rebecca C, Barch Joshua, Cuddapah Sanmati R, DiBoscio Brenda S, DiPerna James C, Gordon Patricia L, Henderson Nadene, Menello Caitlin, Luongo Nicole, Ortiz Damara, Xiao Rui
Division of Human Genetics/Metabolism, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Pediatrics, Division of Medical Genetics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
Int J Neonatal Screen. 2020 Nov 13;6(4):89. doi: 10.3390/ijns6040089.
Pennsylvania started newborn screening for Pompe disease in February 2016. Between February 2016 and December 2019, 531,139 newborns were screened. Alpha-Glucosidase (GAA) enzyme activity is measured by flow-injection tandem mass spectrometry (FIA/MS/MS) and full sequencing of the GAA gene is performed as a second-tier test in all newborns with low GAA enzyme activity [<2.10 micromole/L/h]. A total of 115 newborns had low GAA enzyme activity and abnormal genetic testing and were referred to metabolic centers. Two newborns were diagnosed with Infantile Onset Pompe Disease (IOPD), and 31 newborns were confirmed to have Late Onset Pompe Disease (LOPD). The incidence of IOPD + LOPD was 1:16,095. A total of 30 patients were compound heterozygous for one pathogenic and one variant of unknown significance (VUS) mutation or two VUS mutations and were defined as suspected LOPD. The incidence of IOPD + LOPD + suspected LOPD was 1: 8431 in PA. We also found 35 carriers, 15 pseudodeficiency carriers, and 2 false positive newborns.
宾夕法尼亚州于2016年2月开始对庞贝病进行新生儿筛查。在2016年2月至2019年12月期间，共对531,139名新生儿进行了筛查。通过流动注射串联质谱法（FIA/MS/MS）测量α-葡萄糖苷酶（GAA）的酶活性，并对所有GAA酶活性低[<2.10微摩尔/升/小时]的新生儿进行GAA基因的全序列测定作为二级检测。共有115名新生儿GAA酶活性低且基因检测异常，并被转诊至代谢中心。两名新生儿被诊断为婴儿型庞贝病（IOPD），31名新生儿被确诊为晚发型庞贝病（LOPD）。IOPD + LOPD的发病率为1:16,095。共有30名患者为一个致病突变和一个意义未明的变异（VUS）突变或两个VUS突变的复合杂合子，被定义为疑似LOPD。在宾夕法尼亚州，IOPD + LOPD +疑似LOPD的发病率为1:8431。我们还发现了35名携带者、15名假缺陷携带者和2名假阳性新生儿。
