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

An Erratum to this article was published on 21 November 2014

Abstract

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.

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Abbreviations

AC:

Acylcarnitine

BPM:

Beats Per Minute

CV:

Coefficient of variation

DHA:

Docosahexaenoic acid

FAOD:

Fatty acid oxidation disorders

GC-MS:

Gas chromatography–mass spectrometry

GH:

Growth hormone

LCHAD deficiency:

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

LCT:

Long-chain triglyceride

MCT fat:

Medium-chain triglyceride fat

NEFA:

Non-esterified fatty acids

REE:

Resting energy expenditure

TAG:

Tri-acyl-glycerol

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Acknowledgments

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

None.

Human or animal studies

Informed consent was obtained from all families.

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Correspondence to C. Bieneck Haglind.

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Communicated by: Piero Rinaldo

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Haglind, C.B., Nordenström, A., Ask, S. et al. Increased and early lipolysis in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency during fast. J Inherit Metab Dis 38, 315–322 (2015). https://doi.org/10.1007/s10545-014-9750-3

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  • DOI: https://doi.org/10.1007/s10545-014-9750-3

Keywords

  • Subcutaneous Adipose Tissue
  • Fasting Period
  • Glycerol Production
  • Metabolic Decompensation
  • Fatty Acid Accumulation