Serum C14:1/C12:1 ratio is a useful marker for differentiating affected patients with very long-chain acyl-CoA dehydrogenase deficiency from heterozygous carriers

• Main Authors: Kenji Yamada, Yoshimitsu Osawa, Hironori Kobayashi, Yuki Hasegawa, Seiji Fukuda, Seiji Yamaguchi, Takeshi Taketani
• Format: Article
• Language: English
• Published: Elsevier 2019-12-01
• Series: Molecular Genetics and Metabolism Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2214426919301831

Introduction: Various markers, such as C14:1 and the C14:1/C2 ratio, are used as diagnostic markers of very long-chain acyl-CoA dehydrogenase deficiency (VLCADD). However, the levels of these markers in patients with VLCADD overlap with those in heterozygous carriers and even healthy subjects. Materials and methods: In twenty-three affected patients and 15 heterozygous carriers with VLCADD, the accuracies of C14:1, C14:1/C12:1, C14:1/C2, and C14:1/C16 in dried blood spots (DBS) and serum were statistically estimated. Results: Among the serum markers, the sensitivity, specificity, positive predictive value, negative predictive value, false-positive rate, false-negative rate, and validity of C14:1/C12:1 were superior to those of C14:1, C14:1/C2, and C14:1/C16, but C14:1/C2 demonstrated a statistical advantage compared with only C14:1 and C14:1/C16. Elevation in serum C14:1/C12:1 was observed in only one heterozygous carrier, whereas almost half of the carriers displayed false positive results for the other markers. Among the DBS markers, although the accuracy of C14:1/C2 was ostensibly the best, no statistical significance was observed. Discussion: Serum C14:1/C12:1 might be useful for differentiating patients with VLCADD from heterozygous carriers. Although serum C14:1/C2 was significantly useful for the detection of VLCADD, this marker could not distinguish the affected patients from carriers. C14:1/C12:1 might be optimal compared with the other markers. Keywords: Very long-chain acyl-CoA dehydrogenase deficiency, Tetradecenoyl carnitine, Dodecenoyl carnitine, Heterozygous carrier, Newborn screening, Diagnostic markers