Using the C14:1/Medium-Chain Acylcarnitine Ratio Instead of C14:1 to Reduce False-Positive Results for Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency in Newborn Screening in Japan

Go Tajima; Junko Aisaki; Keiichi Hara; Miyuki Tsumura; Reiko Kagawa; Fumiaki Sakura; Hideo Sasai; Miori Yuasa; Yosuke Shigematsu; Satoshi Okada

doi:10.3390/ijns10010015

Using the C14:1/Medium-Chain Acylcarnitine Ratio Instead of C14:1 to Reduce False-Positive Results for Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency in Newborn Screening in Japan

Int J Neonatal Screen. 2024 Feb 20;10(1):15. doi: 10.3390/ijns10010015.

Authors

Go Tajima^{1

2}, Junko Aisaki¹, Keiichi Hara^{2

3}, Miyuki Tsumura², Reiko Kagawa², Fumiaki Sakura^{2

4}, Hideo Sasai⁵, Miori Yuasa⁶, Yosuke Shigematsu⁶, Satoshi Okada²

Affiliations

¹ Division of Neonatal Screening, Research Institute, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
² Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
³ Department of Pediatrics, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure 737-0023, Japan.
⁴ Department of Technology Development, Kazusa DNA Research Institute, 2-6-7 Kazusa-kamatari, Kisarazu 292-0818, Japan.
⁵ Department of Early Diagnosis and Preventive Medicine for Rare Intractable Pediatric Diseases, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
⁶ Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji-cho 910-1193, Japan.

Abstract

Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a long-chain fatty acid oxidation disorder that manifests as either a severe phenotype associated with cardiomyopathy, a hypoglycemic phenotype, or a myopathic phenotype. As the hypoglycemic phenotype can cause sudden infant death, VLCAD deficiency is included in newborn screening (NBS) panels in many countries. The tetradecenoylcarnitine (C14:1) level in dried blood specimens is commonly used as a primary marker for VLCAD deficiency in NBS panels. Its ratio to acetylcarnitine (C2) and various other acylcarnitines is used as secondary markers. In Japan, tandem mass spectrometry-based NBS, initially launched as a pilot study in 1997, was introduced to the nationwide NBS program in 2013. In the present study, we evaluated levels of acylcarnitine with various chain lengths (C18 to C2), free carnitine, and their ratios in 175 infants who tested positive for VLCAD deficiency with C14:1 and C14:1/C2 ratios. Our analyses indicated that the ratios of C14:1 to medium-chain acylcarnitines (C10, C8, and C6) were the most effective markers in reducing false-positive rates. Their use with appropriate cutoffs is expected to improve NBS performance for VLCAD deficiency.

Keywords: ACADVL; acylcarnitine ratio; decanoylcarnitine (C10); false-positive; hexanoylcarnitine (C6); newborn screening; octanoylcarnitine (C8); tetradecenoylcarnitine (C14:1); very-long-chain acyl-CoA dehydrogenase.

Abstract

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