Journal of Inherited Metabolic Disease

, Volume 38, Issue 2, pp 315–322 | Cite as

Increased and early lipolysis in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency during fast

  • C. Bieneck Haglind
  • A. Nordenström
  • S. Ask
  • U. von Döbeln
  • J. Gustafsson
  • M. Halldin Stenlid
Original Article


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.


Subcutaneous Adipose Tissue Fasting Period Glycerol Production Metabolic Decompensation Fatty Acid Accumulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





Beats Per Minute


Coefficient of variation


Docosahexaenoic acid


Fatty acid oxidation disorders


Gas chromatography–mass spectrometry


Growth hormone

LCHAD deficiency

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency


Long-chain triglyceride

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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Copyright information

© SSIEM 2014

Authors and Affiliations

  • C. Bieneck Haglind
    • 1
  • A. Nordenström
    • 1
  • S. Ask
    • 3
  • U. von Döbeln
    • 2
  • J. Gustafsson
    • 4
  • M. Halldin Stenlid
    • 4
  1. 1.Women’s and Children’s HealthKarolinska InstituteStockholmSweden
  2. 2.Division of Metabolic Diseases, Department of Laboratory MedicineKarolinska InstituteStockholmSweden
  3. 3.Astrid Lindgren Children’s HospitalKarolinska University HospitalStockholmSweden
  4. 4.Department of Women’s and Children’s HealthUniversity Children’s HospitalUppsalaSweden

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