Severity estimation of very-long-chain acyl-CoA dehydrogenase deficiency via 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-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 C-C2/C-C18 and C-C12/C-C14 ratios in the U-C-stearic acid loading test and in the C-C2/C-C18:1 and C-C12:1/C-C14:1 ratios in the U-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 C-C16/C-C18 ratio than the C-C14/C-C18 ratio in the U-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-C-oleic acid loading test was useful for comparing the patient group with the control group in terms of disease severity. The U-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.