Abstract
Background: 3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCd) is an autosomal recessive disorder in the catabolism of leucine. In the present study, we investigated the current and prior medical condition of patients with 3-MCCd in the Faroe Islands and their carnitine levels in blood, urine and muscle tissue with and without l-carnitine supplementation to evaluate the current treatment strategy of not recommending l-carnitine supplementation to Faroese 3-MCCd patients.
Methods: Blood and urine samples and muscle biopsies were collected from patients at inclusion and at 3 months. Eight patients received l-carnitine supplementation when recruited; five did not. Included patients who received supplementation were asked to stop l-carnitine, the others were asked to initiate l-carnitine supplementation during the study. Symptoms were determined by review of hospital medical records and questionnaires answered at baseline and after the intervention.
Results: The prevalence of 3-MCCd in the Faroe Islands was 1:2,400, the highest reported worldwide. All patients were homozygous for the MCCC1 mutation c.1526delG. When not administered l-carnitine, the 3-MCCd patients (n = 13) had low plasma and muscle free carnitine levels, 6.9 (SD 1.4) μmol/L and 785 (SD 301) nmol/g wet weight, respectively. l-Carnitine supplementation increased muscle and plasma carnitine levels to a low-normal range, 25.5 (SD 10.9) μmol/L and 1,827 (SD 523) nmol/g wet weight, p < 0.01, respectively. Seven of the thirteen 3-MCCd subjects suffered from self-reported fatigue with some alleviation after l-carnitine supplementation.
Conclusion: 3-MCCd is common in the Faroe Islands. Some symptomatic 3-MCCd patients may benefit biochemically and clinically from l-carnitine supplementation, a more general recommendation cannot be given.
Competing interests: None declared
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Acknowledgements
The authors would like to thank Tjaldurs Apotek, the Faroese Genetic Biobank, the National Hospital of the Faroe Islands and the University of Copenhagen for their assistance. The authors would also like to thank Mette Christensen, CIMD, for performing the analysis of 3-hydroxyisovaleric acid in urine.
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Communicated by: Piero Rinaldo, MD, PhD
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The project was funded by the Research Committee at the National Hospital, Torshavn, Faroe Islands.
Synopsis
Intramuscular levels of free carnitine correlate with plasma levels of free carnitine and can be restored to near-normal levels with oral l-carnitine supplementation in 3-MCCd patients.
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Jákup Andreas Thomsen, Allan Meldgaard Lund, Jess Have Olesen, Magni Mohr and Jan Rasmussen declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
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Corresponding author Jákup Andreas Thomsen was involved in all aspects of the work and is the guarantor and wrote the article.
Jan Rasmussen has been involved in the conception, design, analysis and interpretation of data and revised the article critically for important intellectual content.
Magni Mohr has been involved in the conception, design and interpretation of data and revised the article critically for important intellectual content.
Jess Have Olesen has been involved in the conception, design, analysis and interpretation of data and revised the article critically for important intellectual content.
Allan Meldgaard Lund has been involved in the conception, design, analysis and interpretation of data and revised the article critically for important intellectual content.
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Thomsen, J.A., Lund, A.M., Olesen, J.H., Mohr, M., Rasmussen, J. (2014). Is l-Carnitine Supplementation Beneficial in 3-Methylcrotonyl-CoA Carboxylase Deficiency?. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 21. JIMD Reports, vol 21. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_393
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DOI: https://doi.org/10.1007/8904_2014_393
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