Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of L-Carnitine Supplementation

J Rasmussen; J A Thomsen; J H Olesen; Trine Meldgaard Lund; M Mohr; J Clementsen; O W Nielsen; A M Lund

doi:10.1007/8904_2014_398

Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of _L-Carnitine Supplementation

J Rasmussen, J A Thomsen, J H Olesen, Trine Meldgaard Lund, M Mohr, J Clementsen, O W Nielsen, A M Lund

Department of Clinical Medicine

9 Citations (Scopus)

Abstract

Background: Primary carnitine deficiency (PCD) is a disorder of fatty acid oxidation with a high prevalence in the Faroe Islands. Only patients homozygous for the c.95A>G (p.N32S) mutation have displayed severe symptoms in the Faroese patient cohort. In this study, we investigated carnitine levels in skeletal muscle, plasma, and urine as well as renal elimination kinetics before and after intermission with l-carnitine in patients homozygous for c.95A>G. Methods: Five male patients homozygous for c.95A>G were included. Regular l-carnitine supplementation was stopped and the patients were observed during five days. Blood and urine were collected throughout the study. Skeletal muscle biopsies were obtained at 0, 48, and 96 h. Results: Mean skeletal muscle free carnitine before discontinuation of l-carnitine was low, 158 nmol/g (SD 47.4) or 5.4% of normal. Mean free carnitine in plasma (fC0) dropped from 38.7 (SD 20.4) to 6.3 (SD 1.7) μmol/L within 96 h (p < 0.05). Mean T _1/2 following oral supplementation was approximately 9 h. Renal reabsorption of filtered carnitine following oral supplementation was 23%. The level of mean free carnitine excreted in urine correlated (R ² = 0.78, p < 0.01) with fC0 in plasma. Conclusion: Patients homozygous for the c.95A>G mutation demonstrated limited skeletal muscle carnitine stores despite long-term high-dosage l-carnitine supplementation. Exacerbated renal excretion resulted in a short T _1/2 in plasma carnitine following the last oral dose of l-carnitine. Thus a treatment strategy of minimum three daily separate doses of l-carnitine is recommended, while intermission with l-carnitine treatment might prove detrimental.

Original language	English
Title of host publication	JIMD Reports
Editors	Johannes Zschocke, Matthias Baumgartner, Eva Morava, Marc Patterson, Shamima Rahman, Verena Peters
Number of pages	9
Volume	20
Place of Publication	Berlin
Publisher	Springer
Publication date	10 Feb 2015
Pages	103-111
ISBN (Print)	978-3-662-46699-5
ISBN (Electronic)	978-3-662-46700-8
DOIs	https://doi.org/10.1007/8904_2014_398
Publication status	Published - 10 Feb 2015

Series	JIMD Reports
ISSN	2192-8304

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10.1007/8904_2014_398

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Rasmussen, J., Thomsen, J. A., Olesen, J. H., Lund, T. M., Mohr, M., Clementsen, J., Nielsen, O. W., & Lund, A. M. (2015). Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of _L-Carnitine Supplementation. In J. Zschocke, M. Baumgartner, E. Morava, M. Patterson, S. Rahman, & V. Peters (Eds.), JIMD Reports (Vol. 20, pp. 103-111). Springer. JIMD Reports https://doi.org/10.1007/8904_2014_398

Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of _L-Carnitine Supplementation. / Rasmussen, J; Thomsen, J A; Olesen, J H et al.

JIMD Reports. ed. / Johannes Zschocke; Matthias Baumgartner; Eva Morava; Marc Patterson; Shamima Rahman; Verena Peters. Vol. 20 Berlin : Springer, 2015. p. 103-111 (JIMD Reports).

Research output: Chapter in Book/Report/Conference proceeding › Book chapter › Research › peer-review

Rasmussen, J, Thomsen, JA, Olesen, JH, Lund, TM, Mohr, M, Clementsen, J, Nielsen, OW & Lund, AM 2015, Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of _L-Carnitine Supplementation. in J Zschocke, M Baumgartner, E Morava, M Patterson, S Rahman & V Peters (eds), JIMD Reports. vol. 20, Springer, Berlin, JIMD Reports, pp. 103-111. https://doi.org/10.1007/8904_2014_398

Rasmussen J, Thomsen JA, Olesen JH, Lund TM, Mohr M, Clementsen J et al. Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of _L-Carnitine Supplementation. In Zschocke J, Baumgartner M, Morava E, Patterson M, Rahman S, Peters V, editors, JIMD Reports. Vol. 20. Berlin: Springer. 2015. p. 103-111. (JIMD Reports). doi: 10.1007/8904_2014_398

Rasmussen, J ; Thomsen, J A ; Olesen, J H et al. / Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of _L-Carnitine Supplementation. JIMD Reports. editor / Johannes Zschocke ; Matthias Baumgartner ; Eva Morava ; Marc Patterson ; Shamima Rahman ; Verena Peters. Vol. 20 Berlin : Springer, 2015. pp. 103-111 (JIMD Reports).

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title = "Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of L-Carnitine Supplementation",

abstract = "Background: Primary carnitine deficiency (PCD) is a disorder of fatty acid oxidation with a high prevalence in the Faroe Islands. Only patients homozygous for the c.95A>G (p.N32S) mutation have displayed severe symptoms in the Faroese patient cohort. In this study, we investigated carnitine levels in skeletal muscle, plasma, and urine as well as renal elimination kinetics before and after intermission with l-carnitine in patients homozygous for c.95A>G. Methods: Five male patients homozygous for c.95A>G were included. Regular l-carnitine supplementation was stopped and the patients were observed during five days. Blood and urine were collected throughout the study. Skeletal muscle biopsies were obtained at 0, 48, and 96 h. Results: Mean skeletal muscle free carnitine before discontinuation of l-carnitine was low, 158 nmol/g (SD 47.4) or 5.4% of normal. Mean free carnitine in plasma (fC0) dropped from 38.7 (SD 20.4) to 6.3 (SD 1.7) μmol/L within 96 h (p < 0.05). Mean T 1/2 following oral supplementation was approximately 9 h. Renal reabsorption of filtered carnitine following oral supplementation was 23%. The level of mean free carnitine excreted in urine correlated (R 2 = 0.78, p < 0.01) with fC0 in plasma. Conclusion: Patients homozygous for the c.95A>G mutation demonstrated limited skeletal muscle carnitine stores despite long-term high-dosage l-carnitine supplementation. Exacerbated renal excretion resulted in a short T 1/2 in plasma carnitine following the last oral dose of l-carnitine. Thus a treatment strategy of minimum three daily separate doses of l-carnitine is recommended, while intermission with l-carnitine treatment might prove detrimental.",

author = "J Rasmussen and Thomsen, {J A} and Olesen, {J H} and Lund, {Trine Meldgaard} and M Mohr and J Clementsen and Nielsen, {O W} and Lund, {A M}",

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T1 - Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of L-Carnitine Supplementation

AU - Rasmussen, J

AU - Thomsen, J A

AU - Olesen, J H

AU - Lund, Trine Meldgaard

AU - Mohr, M

AU - Clementsen, J

AU - Nielsen, O W

AU - Lund, A M

PY - 2015/2/10

Y1 - 2015/2/10

N2 - Background: Primary carnitine deficiency (PCD) is a disorder of fatty acid oxidation with a high prevalence in the Faroe Islands. Only patients homozygous for the c.95A>G (p.N32S) mutation have displayed severe symptoms in the Faroese patient cohort. In this study, we investigated carnitine levels in skeletal muscle, plasma, and urine as well as renal elimination kinetics before and after intermission with l-carnitine in patients homozygous for c.95A>G. Methods: Five male patients homozygous for c.95A>G were included. Regular l-carnitine supplementation was stopped and the patients were observed during five days. Blood and urine were collected throughout the study. Skeletal muscle biopsies were obtained at 0, 48, and 96 h. Results: Mean skeletal muscle free carnitine before discontinuation of l-carnitine was low, 158 nmol/g (SD 47.4) or 5.4% of normal. Mean free carnitine in plasma (fC0) dropped from 38.7 (SD 20.4) to 6.3 (SD 1.7) μmol/L within 96 h (p < 0.05). Mean T 1/2 following oral supplementation was approximately 9 h. Renal reabsorption of filtered carnitine following oral supplementation was 23%. The level of mean free carnitine excreted in urine correlated (R 2 = 0.78, p < 0.01) with fC0 in plasma. Conclusion: Patients homozygous for the c.95A>G mutation demonstrated limited skeletal muscle carnitine stores despite long-term high-dosage l-carnitine supplementation. Exacerbated renal excretion resulted in a short T 1/2 in plasma carnitine following the last oral dose of l-carnitine. Thus a treatment strategy of minimum three daily separate doses of l-carnitine is recommended, while intermission with l-carnitine treatment might prove detrimental.

AB - Background: Primary carnitine deficiency (PCD) is a disorder of fatty acid oxidation with a high prevalence in the Faroe Islands. Only patients homozygous for the c.95A>G (p.N32S) mutation have displayed severe symptoms in the Faroese patient cohort. In this study, we investigated carnitine levels in skeletal muscle, plasma, and urine as well as renal elimination kinetics before and after intermission with l-carnitine in patients homozygous for c.95A>G. Methods: Five male patients homozygous for c.95A>G were included. Regular l-carnitine supplementation was stopped and the patients were observed during five days. Blood and urine were collected throughout the study. Skeletal muscle biopsies were obtained at 0, 48, and 96 h. Results: Mean skeletal muscle free carnitine before discontinuation of l-carnitine was low, 158 nmol/g (SD 47.4) or 5.4% of normal. Mean free carnitine in plasma (fC0) dropped from 38.7 (SD 20.4) to 6.3 (SD 1.7) μmol/L within 96 h (p < 0.05). Mean T 1/2 following oral supplementation was approximately 9 h. Renal reabsorption of filtered carnitine following oral supplementation was 23%. The level of mean free carnitine excreted in urine correlated (R 2 = 0.78, p < 0.01) with fC0 in plasma. Conclusion: Patients homozygous for the c.95A>G mutation demonstrated limited skeletal muscle carnitine stores despite long-term high-dosage l-carnitine supplementation. Exacerbated renal excretion resulted in a short T 1/2 in plasma carnitine following the last oral dose of l-carnitine. Thus a treatment strategy of minimum three daily separate doses of l-carnitine is recommended, while intermission with l-carnitine treatment might prove detrimental.

U2 - 10.1007/8904_2014_398

DO - 10.1007/8904_2014_398

M3 - Book chapter

C2 - 25665836

SN - 978-3-662-46699-5

VL - 20

T3 - JIMD Reports

SP - 103

EP - 111

BT - JIMD Reports

A2 - Zschocke, Johannes

A2 - Baumgartner, Matthias

A2 - Morava, Eva

A2 - Patterson, Marc

A2 - Rahman, Shamima

A2 - Peters, Verena

PB - Springer

CY - Berlin

ER -

Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of L-Carnitine Supplementation

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Carnitine Levels in Skeletal Muscle, Blood, and Urine in Patients with Primary Carnitine Deficiency During Intermission of _L-Carnitine Supplementation