Assessment of Fasting Metabolism With Microdialysis Indicates Earlier Lipolysis in Children With VLCADD Than MCADD

Abstract

Aim

To investigate fasting metabolism in children with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and medium-chain acyl-CoA dehydrogenase deficiency (MCADD) using microdialysis technique.

Methods

Twelve patients (7 with VLCADD, 5 with MCADD, mean age 4.9 years, 10/12 diagnosed via newborn screening) were recruited for investigation in connection to clinical fasting examinations at the Karolinska University Hospital (between 2015 and 2024). Patients were subjected to a 9-h night fast after a standard late evening meal. Analysis of glucose, glycerol, lactate, and pyruvate was conducted by continuous microdialysis. Fasting hormones and acylcarnitines were analysed in blood samples at 1-h intervals in patients with VLCADD.

Results

Children with VLCADD showed signs of lipolysis after a median fasting time of 4.5 h, whereas patients with MCADD showed no significant increase in lipolysis during the fast. A shorter time to initiation of lipolysis tended to correlate with a lower residual enzyme activity in patients with VLCADD. All patients maintained euglycemia during fasting.

Conclusion

Children with VLCADD had a shorter time to initiation of lipolysis during fasting than children with MCADD. Clinical evaluation of fasting metabolism in beta-oxidation disorders should include assessment of lipolysis as an early and important determinant.