Department of Clinical Laboratory, Quanzhou Maternity and Children's Hospital, Quanzhou, Fujian, China.
Neonatal Disease Screening Center, Quanzhou Maternity and Children's Hospital, Quanzhou, Fujian, China.
Mol Genet Genomic Med. 2024 Sep;12(9):e70003. doi: 10.1002/mgg3.70003.
Newborn screening (NBS) for primary carnitine deficiency (PCD) has poor performance. This study aimed to evaluate the feasibility of incorporating next-generation sequencing (NGS) as a second-tier PCD test.
Between March and December 2020, 60,070 newborns were screened for inherited metabolic disorders. Newborns with free carnitine (C0) levels below 8.5 μmol/L were selected for second-tier genetic testing.
In total, 130 (0.22%) newborns with low C0 levels underwent second-tier genetic testing, 87 (66.92%) had positive genetic testing results, and 30 (23.08%) carried pathogenic variants of the SLC22A5 gene. Six newborns were diagnosed with PCD. The incidence of PCD was approximately 1 in 1:10,012 newborns. The PPV reached 20% after combining with second-tier NGS. Of the eight variants identified in patients with PCD, the three most common variants were c.760C>T (p.Arg254*), c.51C>G (p.Phe17Leu), and c.1400C>G (p.Ser467Cys). The C0 levels of patients with PCD were significantly lower than those of PCD carriers (p = 0.0026) and PCD-negative individuals (p = 0.0005).
Our results showed that the PPV reached 20% after combining with second-tier NGS. The MS/MS-based NBS and second-tier NGS combination can effectively reduce the false-positive rate and detect PCD in patients.
新生儿筛查（NBS）在原发性肉碱缺乏症（PCD）中的应用效果不佳。本研究旨在评估将下一代测序（NGS）作为二线 PCD 检测方法的可行性。
2020 年 3 月至 12 月，对 60070 例新生儿进行遗传性代谢疾病筛查。选择游离肉碱（C0）水平低于 8.5μmol/L 的新生儿进行二线基因检测。
共有 130 例（0.22%）C0 水平低的新生儿接受二线基因检测，87 例（66.92%）检测结果阳性，30 例（23.08%）携带 SLC22A5 基因突变。6 例新生儿被诊断为 PCD。PCD 的发病率约为 1:10012。与二线 NGS 联合应用后，PPV 达到 20%。在 8 例 PCD 患者中发现的变异中，最常见的三种变异为 c.760C>T(p.Arg254*)、c.51C>G(p.Phe17Leu)和 c.1400C>G(p.Ser467Cys)。PCD 患者的 C0 水平明显低于 PCD 携带者（p=0.0026）和 PCD 阴性个体（p=0.0005）。
我们的研究结果表明，与二线 NGS 联合应用后，PPV 达到 20%。基于 MS/MS 的 NBS 和二线 NGS 联合应用可以有效降低假阳性率，检测出患者的 PCD。
