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

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- 13 C-) 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 13 C-C2/ 13 C-C18 and 13 C-C12/ 13 C-C14 ratios in the U- 13 C-stearic acid loading test and in the 13 C-C2/ 13 C-C18:1 and 13 C-C12:1/ 13 C-C14:1 ratios in the U- 13 C-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 13 C-C16/ 13 C-C18 ratio than the 13 C-C14/ 13 C-C18 ratio in the U- 13 C-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- 13 C-oleic acid loading test was useful for comparing the patient group with the control group in terms of disease severity. The U- 13 C-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.