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. / Rasmussen, J; Thomsen, J A; Olesen, J H; Lund, Trine Meldgaard; Mohr, M; Clementsen, J; Nielsen, O W; Lund, A M.
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
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TY - CHAP
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 -
ID: 161364676