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Management and outcome in 75 individuals with long-chain fatty acid oxidation defects: results from a workshop

Summary

At present, long-chain fatty acid oxidation (FAO) defects are diagnosed in a number of countries by newborn screening using tandem mass spectrometry. In the majority of cases, affected newborns are asymptomatic at time of diagnosis and acute clinical presentations can be avoided by early preventive measures. Because evidence-based studies on management of long-chain FAO defects are lacking, we carried out a retrospective analysis of 75 patients from 18 metabolic centres in Germany, Switzerland, Austria and the Netherlands with special regard to treatment and disease outcome. Dietary treatment is effective in many patients and can prevent acute metabolic derangements and prevent or reverse severe long-term complications such as cardiomyopathy. However, 38% of patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency had intermittent muscle weakness and pain despite adhering to therapy. Seventy-six per cent of patients with disorders of the mitochondrial trifunctional protein (TFP)-complex including long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, had long-term myopathic symptoms. Of these, 21% had irreversible peripheral neuropathy and 43% had retinopathy. The main principle of treatment was a fat-reduced and fat-modified diet. Fat restriction differed among patients with different enzyme defects and was strictest in disorders of the TFP-complex. Patients with a medium-chain fat-based diet received supplementation of essential long-chain fatty acids. l-Carnitine was supplemented in about half of the patients, but in none of the patients with VLCAD deficiency identified by newborn screening. In summary, in this cohort the treatment regimen was adapted to the severity of the underlying enzyme defect and thus differed among the group of long-chain FAO defects.

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Fig. 1

Abbreviations

CPT II(D):

carnitine palmitoyl transferase II (deficiency)

FAO:

fatty acid oxidation

LCHAD(D):

long-chain 3-hydroxy-acyl-CoA dehydrogenase (deficiency)

LCT:

long-chain triglycerides (long-chain fat)

LKAT(D):

long-chain 3-ketoacyl-CoA thiolase (deficiency)

MCT:

medium-chain triglycerides

TFP(D):

mitochondrial trifunctional protein (deficiency)

VLCAD(D):

very long-chain acyl-CoA dehydrogenase (deficiency)

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Acknowledgements

The authors thank Milupa Metabolics for sponsoring this workshop on this group of inherited metabolic diseases. The authors also thank the other participants of the study group.

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Correspondence to U. Spiekerkoetter.

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Competing interests: None declared

Communicating editor: Bridget Wilcken

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Spiekerkoetter, U., Lindner, M., Santer, R. et al. Management and outcome in 75 individuals with long-chain fatty acid oxidation defects: results from a workshop. J Inherit Metab Dis 32, 488–497 (2009). https://doi.org/10.1007/s10545-009-1125-9

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  • DOI: https://doi.org/10.1007/s10545-009-1125-9

Keywords

  • Newborn Screening
  • Free Carnitine
  • Newborn Screening Programme
  • Neuropathic Symptom
  • Fatty Acid Oxidation Defect