Journal of Inherited Metabolic Disease

, Volume 32, Issue 4, pp 488–497

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

  • U. Spiekerkoetter
  • M. Lindner
  • R. Santer
  • M. Grotzke
  • M. R. Baumgartner
  • H. Boehles
  • A. Das
  • C. Haase
  • J. B. Hennermann
  • D. Karall
  • H. de Klerk
  • I. Knerr
  • H. G. Koch
  • B. Plecko
  • W. Röschinger
  • K. O. Schwab
  • D. Scheible
  • F. A. Wijburg
  • J. Zschocke
  • E. Mayatepek
  • U. Wendel
Original Article

DOI: 10.1007/s10545-009-1125-9

Cite this article as:
Spiekerkoetter, U., Lindner, M., Santer, R. et al. J Inherit Metab Dis (2009) 32: 488. doi:10.1007/s10545-009-1125-9

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.

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)

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • U. Spiekerkoetter
    • 1
  • M. Lindner
    • 2
  • R. Santer
    • 3
  • M. Grotzke
    • 1
  • M. R. Baumgartner
    • 4
  • H. Boehles
    • 5
  • A. Das
    • 6
  • C. Haase
    • 7
  • J. B. Hennermann
    • 8
  • D. Karall
    • 9
  • H. de Klerk
    • 10
  • I. Knerr
    • 11
  • H. G. Koch
    • 12
  • B. Plecko
    • 13
  • W. Röschinger
    • 14
  • K. O. Schwab
    • 15
  • D. Scheible
    • 16
  • F. A. Wijburg
    • 17
  • J. Zschocke
    • 18
  • E. Mayatepek
    • 1
  • U. Wendel
    • 1
  1. 1.Department of General PediatricsUniversity Children’s HospitalDüsseldorfGermany
  2. 2.Department of PediatricsUniversity Children’s HospitalHeidelbergGermany
  3. 3.Department of PediatricsUniversity Medical Center Hamburg-EppendorfHamburgGermany
  4. 4.Department of PediatricsUniversity Children’s HospitalZürichSwitzerland
  5. 5.Department of PediatricsUniversity Children’s HospitalFrankfurtGermany
  6. 6.Department of PediatricsUniversity Children’s HospitalHannoverGermany
  7. 7.Department of PediatricsUniversity Children’s HospitalJenaGermany
  8. 8.Otto-Heubner-Center for Pediatric and Adolescent MedicineCharité UniversitätsmedizinBerlinGermany
  9. 9.Department of PediatricsUniversity Children’s HospitalInnsbruckAustria
  10. 10.Department of PediatricsUniversity of RotterdamRotterdamThe Netherlands
  11. 11.Department of PediatricsUniversity Children’s HospitalErlangenGermany
  12. 12.Department of PediatricsUniversity Children’s Hospital, Münster and Children’s HospitalBraunschweigGermany
  13. 13.Department of PediatricsUniversity Children’s HospitalGrazAustria
  14. 14.Department of PediatricsUniversity Children’s HospitalMünichGermany
  15. 15.Department of PediatricsUniversity Children’s HospitalFreiburgGermany
  16. 16.Children’s HospitalReutlingenGermany
  17. 17.Department of PediatricsUniversity of AmsterdamAmsterdamThe Netherlands
  18. 18.Human Genetics and Clinical GeneticsMedical University InnsbruckInnsbruckAustria