Newborn screening for primary carnitine deficiency using a second-tier genetic test

Yiming Lin; Chunmei Lin; Zhenzhu Zheng; Chenggang Huang; Weilin Peng

doi:10.1515/jpem-2023-0513

Article

Newborn screening for primary carnitine deficiency using a second-tier genetic test

Yiming Lin , Chunmei Lin , Zhenzhu Zheng , Chenggang Huang and Weilin Peng

Published/Copyright: January 1, 2024

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 2

Abstract

Objectives

Newborn screening (NBS) for primary carnitine deficiency (PCD) exhibits suboptimal performance. This study proposes a strategy to enhance the efficacy of second-tier genetic screening by adjusting the cutoff value for free carnitine (C0).

Methods

Between January 2021 and December 2022, we screened 119,898 neonates for inborn metabolic disorders. Neonates with C0 levels below 12 μmol/L were randomly selected for second-tier genetic screening, employing a novel matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) assay.

Results

In total, 2,515 neonates with C0 <12 μmol/L underwent further screening, including 206 neonates with C0 <8.5 μmol/L and 320 neonates with 8.5<C0<12 μmol/L. Genetic screening identified positive results in 12.36 % (65) of neonates, with one being homozygous, 10 compound heterozygotes, and 54 heterozygotes. Sanger sequencing revealed a second SLC22A5 variant in three of the 54 neonates. Ultimately, 14 patients were diagnosed with PCD; all 14 patients exhibited low C0 levels, though two had normal C0 levels during the recall review. The MALDI-TOF MS assay demonstrated detection and diagnostic rates of 89.29 % and 78.57 %, respectively. Eleven distinct SLC22A5 variants were identified, with the most common variant being c.51C>G, accounting for 25 % (7/28) of allelic frequencies.

Conclusions

A novel MALDI-TOF MS assay targeting 21 SLC22A5 variants in a Chinese population was successfully established. This assay exhibits a high detection and diagnostic rate, making it suitable for population-based genetic screening. Combined genetic screening is recommended to enhance the efficiency of PCD–NBS.

Keywords: primary carnitine deficiency; newborn screening; free carnitine; second-tier screening; matrix-assisted laser desorption/ionization-time of flight mass spectrometry

Corresponding author: Weilin Peng, Department of Clinical Laboratory, Quanzhou Maternity and Children’s Hospital, 700 Fengze Street, Quanzhou, Fujian Province 362000, P.R. China, E-mail: wellpeng@163.com

Funding source: Fujian Provincial Society of Laboratory Medicine and National (Fujian) Genetic Testing Technology Application Demonstration Center

Award Identifier / Grant number: 2023LHYC040

Funding source: Quanzhou City Science and Technology Program of China

Award Identifier / Grant number: 2021C052R

Funding source: Joint Innovation Project of Huaqiao University

Award Identifier / Grant number: 2021YX003

Funding source: Natural Science Foundation of Fujian Province

Award Identifier / Grant number: 2021J01538

Acknowledgments

We thank all the participants for their help and support. We would like to thank Editage (www.editage.cn) for the English language editing.

Research ethics: This study received approvalby the Ethics Committee of Quanzhou Maternity and Children’s Hospital (reference number: 2021-IRB-029).
Informed consent: Informed consent was obtained from all individuals included in this study.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Research funding: This work was supported by grants from Fujian Provincial Society of Laboratory Medicine and National (Fujian) Genetic Testing Technology Application Demonstration Center (2023LHYC040), Quanzhou City Science and Technology Program of China (Grant No. 2021C052R), and Joint Innovation Project of Huaqiao University (Grant No. 2021YX003).
Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Received: 2023-11-16

Accepted: 2023-12-18

Published Online: 2024-01-01

Published in Print: 2024-02-26

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Articles in the same Issue

https://doi.org/10.1515/jpem-2023-0513

Keywords for this article

primary carnitine deficiency; newborn screening; free carnitine; second-tier screening; matrix-assisted laser desorption/ionization-time of flight mass spectrometry