Carnitine Profile and Effect of Suppletion in Children with Renal Fanconi Syndrome due to Cystinosis

Background: Cystinosis is an autosomal recessive disorder marked by intralysosomal cystine accumulation. Patients present with generalized proximal tubular dysfunction called renal Fanconi syndrome. Urinary carnitine loss results in plasma and muscle carnitine deficiency, but no clinical signs of ca...

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Main Authors: Besouw, M., Cornelissen, E., Cassiman, D., Kluijtmans, L., van den Heuvel, L., Levtchenko, E.
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Language:English
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Carnitine Deficiency
Carnitine Level
Carnitine Supplementation
Free Carnitine
Total Carnitine
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Cornelissen, E.
Cassiman, D.
Kluijtmans, L.
van den Heuvel, L.
Levtchenko, E.
description Background: Cystinosis is an autosomal recessive disorder marked by intralysosomal cystine accumulation. Patients present with generalized proximal tubular dysfunction called renal Fanconi syndrome. Urinary carnitine loss results in plasma and muscle carnitine deficiency, but no clinical signs of carnitine deficiency have been described. Also, the optimal dose of carnitine supplementation is undefined. This study aimed to determine whether currently recommended carnitine doses result in adequate correction of plasma carnitine. Methods: Five cystinosis patients with renal Fanconi syndrome, aged 2–18 years, were included. l-carnitine was prescribed 50 mg/kg/day since diagnosis: median 36 (range 18–207) months. Total and free plasma and urine carnitine and carnitine profiles were measured at study onset, after stopping l-carnitine for 3 months and 3 months after reintroducing l-carnitine 50 mg/kg/day. Results: At study onset, plasma free carnitine was normal in all patients, total carnitine (1/5), acetylcarnitine (3/5), and several short- and medium-chain acylcarnitines ≤10 carbons (5/5) were increased indicating carnitine over-supplementation. Three months after cessation, carnitine profiles normalized and 3/5 patients showed plasma carnitine deficiency. Three months after reintroduction, plasma free carnitine normalized in all patients, however, carnitine profiles were disturbed in 4/5 patients. Urine free carnitine, acetylcarnitine, and acylcarnitines ≤10 carbons were increased in all patients independent of carnitine supplementation. Conclusion: Administration of recommended doses l-carnitine (50 mg/kg/day) resulted in over-supplementation. Although the drug is considered to be rather safe, long-term effects of over-supplementation remain unknown warranting cautious use of high doses. Plasma carnitine profile might be used as a monitor, to prevent overdosing.
doi_str_mv 10.1007/8904_2014_312
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Michael ; Zschocke, Johannes ; Brown, Garry ; Morava, Eva</contributor><creatorcontrib>Besouw, M. ; Cornelissen, E. ; Cassiman, D. ; Kluijtmans, L. ; van den Heuvel, L. ; Levtchenko, E. ; Peters, Verena ; Gibson, K. Michael ; Zschocke, Johannes ; Brown, Garry ; Morava, Eva</creatorcontrib><description>Background: Cystinosis is an autosomal recessive disorder marked by intralysosomal cystine accumulation. Patients present with generalized proximal tubular dysfunction called renal Fanconi syndrome. Urinary carnitine loss results in plasma and muscle carnitine deficiency, but no clinical signs of carnitine deficiency have been described. Also, the optimal dose of carnitine supplementation is undefined. This study aimed to determine whether currently recommended carnitine doses result in adequate correction of plasma carnitine. Methods: Five cystinosis patients with renal Fanconi syndrome, aged 2–18 years, were included. l-carnitine was prescribed 50 mg/kg/day since diagnosis: median 36 (range 18–207) months. Total and free plasma and urine carnitine and carnitine profiles were measured at study onset, after stopping l-carnitine for 3 months and 3 months after reintroducing l-carnitine 50 mg/kg/day. Results: At study onset, plasma free carnitine was normal in all patients, total carnitine (1/5), acetylcarnitine (3/5), and several short- and medium-chain acylcarnitines ≤10 carbons (5/5) were increased indicating carnitine over-supplementation. Three months after cessation, carnitine profiles normalized and 3/5 patients showed plasma carnitine deficiency. Three months after reintroduction, plasma free carnitine normalized in all patients, however, carnitine profiles were disturbed in 4/5 patients. Urine free carnitine, acetylcarnitine, and acylcarnitines ≤10 carbons were increased in all patients independent of carnitine supplementation. Conclusion: Administration of recommended doses l-carnitine (50 mg/kg/day) resulted in over-supplementation. Although the drug is considered to be rather safe, long-term effects of over-supplementation remain unknown warranting cautious use of high doses. Plasma carnitine profile might be used as a monitor, to prevent overdosing.</description><identifier>ISSN: 2192-8304</identifier><identifier>ISBN: 9783662445860</identifier><identifier>ISBN: 3662445867</identifier><identifier>EISSN: 2192-8312</identifier><identifier>EISBN: 3662445875</identifier><identifier>EISBN: 9783662445877</identifier><identifier>DOI: 10.1007/8904_2014_312</identifier><identifier>PMID: 24798266</identifier><language>eng</language><publisher>Berlin, Heidelberg: Springer Berlin Heidelberg</publisher><subject>Carnitine Deficiency ; Carnitine Level ; Carnitine Supplementation ; Free Carnitine ; Total Carnitine</subject><ispartof>JIMD Reports Volume 16, 2014, Vol.16, p.25-30</ispartof><rights>SSIEM and Springer-Verlag Berlin Heidelberg 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-73512e4fb0decbf4f9be83741b7902c40cdb1124156ed99a71ccbbb852ecd8be3</citedby><relation>JIMD Reports</relation></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221611/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221611/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,733,785,786,790,799,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24798266$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Peters, Verena</contributor><contributor>Gibson, K. Michael</contributor><contributor>Zschocke, Johannes</contributor><contributor>Brown, Garry</contributor><contributor>Morava, Eva</contributor><creatorcontrib>Besouw, M.</creatorcontrib><creatorcontrib>Cornelissen, E.</creatorcontrib><creatorcontrib>Cassiman, D.</creatorcontrib><creatorcontrib>Kluijtmans, L.</creatorcontrib><creatorcontrib>van den Heuvel, L.</creatorcontrib><creatorcontrib>Levtchenko, E.</creatorcontrib><title>Carnitine Profile and Effect of Suppletion in Children with Renal Fanconi Syndrome due to Cystinosis</title><title>JIMD Reports Volume 16</title><addtitle>JIMD Rep</addtitle><description>Background: Cystinosis is an autosomal recessive disorder marked by intralysosomal cystine accumulation. Patients present with generalized proximal tubular dysfunction called renal Fanconi syndrome. Urinary carnitine loss results in plasma and muscle carnitine deficiency, but no clinical signs of carnitine deficiency have been described. Also, the optimal dose of carnitine supplementation is undefined. This study aimed to determine whether currently recommended carnitine doses result in adequate correction of plasma carnitine. Methods: Five cystinosis patients with renal Fanconi syndrome, aged 2–18 years, were included. l-carnitine was prescribed 50 mg/kg/day since diagnosis: median 36 (range 18–207) months. Total and free plasma and urine carnitine and carnitine profiles were measured at study onset, after stopping l-carnitine for 3 months and 3 months after reintroducing l-carnitine 50 mg/kg/day. Results: At study onset, plasma free carnitine was normal in all patients, total carnitine (1/5), acetylcarnitine (3/5), and several short- and medium-chain acylcarnitines ≤10 carbons (5/5) were increased indicating carnitine over-supplementation. Three months after cessation, carnitine profiles normalized and 3/5 patients showed plasma carnitine deficiency. Three months after reintroduction, plasma free carnitine normalized in all patients, however, carnitine profiles were disturbed in 4/5 patients. Urine free carnitine, acetylcarnitine, and acylcarnitines ≤10 carbons were increased in all patients independent of carnitine supplementation. Conclusion: Administration of recommended doses l-carnitine (50 mg/kg/day) resulted in over-supplementation. Although the drug is considered to be rather safe, long-term effects of over-supplementation remain unknown warranting cautious use of high doses. 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Patients present with generalized proximal tubular dysfunction called renal Fanconi syndrome. Urinary carnitine loss results in plasma and muscle carnitine deficiency, but no clinical signs of carnitine deficiency have been described. Also, the optimal dose of carnitine supplementation is undefined. This study aimed to determine whether currently recommended carnitine doses result in adequate correction of plasma carnitine. Methods: Five cystinosis patients with renal Fanconi syndrome, aged 2–18 years, were included. l-carnitine was prescribed 50 mg/kg/day since diagnosis: median 36 (range 18–207) months. Total and free plasma and urine carnitine and carnitine profiles were measured at study onset, after stopping l-carnitine for 3 months and 3 months after reintroducing l-carnitine 50 mg/kg/day. Results: At study onset, plasma free carnitine was normal in all patients, total carnitine (1/5), acetylcarnitine (3/5), and several short- and medium-chain acylcarnitines ≤10 carbons (5/5) were increased indicating carnitine over-supplementation. Three months after cessation, carnitine profiles normalized and 3/5 patients showed plasma carnitine deficiency. Three months after reintroduction, plasma free carnitine normalized in all patients, however, carnitine profiles were disturbed in 4/5 patients. Urine free carnitine, acetylcarnitine, and acylcarnitines ≤10 carbons were increased in all patients independent of carnitine supplementation. Conclusion: Administration of recommended doses l-carnitine (50 mg/kg/day) resulted in over-supplementation. Although the drug is considered to be rather safe, long-term effects of over-supplementation remain unknown warranting cautious use of high doses. Plasma carnitine profile might be used as a monitor, to prevent overdosing.</abstract><cop>Berlin, Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>24798266</pmid><doi>10.1007/8904_2014_312</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Carnitine Deficiency
Carnitine Level
Carnitine Supplementation
Free Carnitine
Total Carnitine
title Carnitine Profile and Effect of Suppletion in Children with Renal Fanconi Syndrome due to Cystinosis
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