Severity estimation of very-long-chain acyl-CoA dehydrogenase deficiency via 13C-fatty acid loading test.

Abstract

BACKGROUND:

The clinical severity of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is difficult to predict using conventional diagnostic methods.

METHODS:

Peripheral blood mononuclear cells obtained from 14 VLCAD deficiency patients and 23 healthy adults were loaded with carbon-13-universally labeled (U-13C-) fatty acids. Differences in acylcarnitine ratios between the patients and healthy groups and correlations between acylcarnitine ratios and a newly established clinical severity score (CSS) in the patient group were statistically examined.

RESULTS:

There was a significant decrease in the 13C-C2/13C-C18 and 13C-C12/13C-C14 ratios in the U-13C-stearic acid loading test and in the 13C-C2/13C-C18:1 and 13C-C12:1/13C-C14:1 ratios in the U-13C-oleic acid loading test in the patient group. The values of each ratio were significantly correlated with the CSS, suggesting that they could predict disease severity. Additionally, patients with a higher 13C-C16/13C-C18 ratio than the 13C-C14/13C-C18 ratio in the U-13C-stearic acid loading test had a significantly higher CSS and were presumed to have more severe disease.

CONCLUSIONS:

Our data indicated that this method could be used to predict the clinical severity of VLCAD deficiency, and identify patients at a risk of severe disease.

IMPACT:

We established a novel method to predict the severity of VLCAD deficiency by performing a loading test with carbon-13-labeled fatty acids on peripheral blood mononuclear cells. The U-13C-oleic acid loading test was useful for comparing the patient group with the control group in terms of disease severity. The U-13C-stearic acid loading test was useful for identifying the more severely affected patients. These methods are relatively less invasive and enable rapid evaluation of the clinical severity.

• Authors: Keiichi Sugihara, Miori Yuasa, Yuko Isozaki, Ikue Hata, Yusei Ohshima, Takashi Hamazaki, Toshihiko Kakiuchi, Masato Arao, Noboru Igarashi, Yumiko Kotani, Tokiko Fukuda, Reiko Kagawa, Go Tajima, Yosuke Shigematsu
• Journal: Pediatric research (Pediatr Res) Vol. 92 Issue 5 Pg. 1391-1399 (11 2022) ISSN: 1530-0447 [Electronic] United States
• PMID: 35136200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

Chemical References

• Carbon-13
• acylcarnitine
• Carnitine
• Fatty Acids
• Stearic Acids
• Oleic Acids

Topics

• Adult
• Humans
• Leukocytes, Mononuclear
• Carnitine
• Fatty Acids
• Stearic Acids
• Oleic Acids