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

Kenji Yamada; Yoshimitsu Osawa; Hironori Kobayashi; Yuki Hasegawa; Seiji Fukuda; Seiji Yamaguchi; Takeshi Taketani

doi:10.1016/j.ymgmr.2019.100535

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

Mol Genet Metab Rep. 2019 Nov 5:21:100535. doi: 10.1016/j.ymgmr.2019.100535. eCollection 2019 Dec.

Authors

Kenji Yamada¹, Yoshimitsu Osawa^{1

2}, Hironori Kobayashi¹, Yuki Hasegawa¹, Seiji Fukuda¹, Seiji Yamaguchi¹, Takeshi Taketani¹

Affiliations

¹ Department of Pediatrics, Shimane University Faculty of Medicine, 89-1 En-ya-cho, Izumo, Shimane 693-8501, Japan.
² Department of Pediatrics, Graduate School of Medicine, Gunma University, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.

Abstract

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: Diagnostic markers; Dodecenoyl carnitine; Heterozygous carrier; Newborn screening; Tetradecenoyl carnitine; Very long-chain acyl-CoA dehydrogenase deficiency.