Increased and early lipolysis in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency during fast
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Children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) have a defect in the degradation of long-chain fatty acids and are at risk of hypoketotic hypoglycemia and insufficient energy production as well as accumulation of toxic fatty acid intermediates. Knowledge on substrate metabolism in children with LCHAD deficiency during fasting is limited. Treatment guidelines differ between centers, both as far as length of fasting periods and need for night feeds are concerned. To increase the understanding of fasting intolerance and improve treatment recommendations, children with LCHAD deficiency were investigated with stable isotope technique, microdialysis, and indirect calometry, in order to assess lipolysis and glucose production during 6 h of fasting. We found an early and increased lipolysis and accumulation of long chain acylcarnitines after 4 h of fasting, albeit no patients developed hypoglycemia. The rate of glycerol production, reflecting lipolysis, averaged 7.7 ± 1.6 µmol/kg/min, which is higher compared to that of peers. The rate of glucose production was normal for age; 19.6 ± 3.4 µmol/kg/min (3.5 ± 0.6 mg/kg/min). Resting energy expenditure was also normal, even though the respiratory quotient was increased indicating mainly glucose oxidation. The results show that lipolysis and accumulation of long chain acylcarnitines occurs before hypoglycemia in fasting children with LCHAD, which may indicate more limited fasting tolerance than previously suggested.
KeywordsSubcutaneous Adipose Tissue Fasting Period Glycerol Production Metabolic Decompensation Fatty Acid Accumulation
Beats Per Minute
Coefficient of variation
Fatty acid oxidation disorders
Gas chromatography–mass spectrometry
- LCHAD deficiency
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
- MCT fat
Medium-chain triglyceride fat
Non-esterified fatty acids
Resting energy expenditure
We express our gratitude to the children and their families for taking part in the study. We are indebted to all our collaborators; Siw Siljerud, Sindra Isetun, Martin Engvall, Sten Salomonsson, Roger Olsson and Elisabeth Söderberg for skillful laboratory and technical expertise, nurses Jenny Gårdman, Jaana Nejla, Kerstin Ekbom, Karin Johansson, and Gunilla Wallin for excellent assistance and patient care. We thank associate Professor Jan Alm and Professor Antal Nemeth for valuable contributions. The study was supported by grants from the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and the Karolinska Institute and Uppsala County and Uppsala University, The Sven Jerring Foundation, The Samariten Foundation, The Child Care Society, The Gillberg foundation and Vera Ekström Foundation.
Compliance with ethical guidelines
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Ethics Committee of Uppsala University, Sweden, decision number 2006/005, 2009-09-30).
Conflict of interest
Human or animal studies
Informed consent was obtained from all families.
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