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Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD

OBJECTIVES: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a severe inborn disorder of mitochondrial fatty acid oxidation. The only treatment option for MADD is the use of exogenous ketone bodies, like sodium β-hydroxybutyrate (NaβHB). However, the use of ketone body salts leads to a high inta...

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Autores principales: Fischer, Tobias, Elpers, Christiane, Och, Ulrike, Fobker, Manfred, Marquardt, Thorsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610240/
https://www.ncbi.nlm.nih.gov/pubmed/31312603
http://dx.doi.org/10.1016/j.ymgmr.2019.100491
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author Fischer, Tobias
Elpers, Christiane
Och, Ulrike
Fobker, Manfred
Marquardt, Thorsten
author_facet Fischer, Tobias
Elpers, Christiane
Och, Ulrike
Fobker, Manfred
Marquardt, Thorsten
author_sort Fischer, Tobias
collection PubMed
description OBJECTIVES: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a severe inborn disorder of mitochondrial fatty acid oxidation. The only treatment option for MADD is the use of exogenous ketone bodies, like sodium β-hydroxybutyrate (NaβHB). However, the use of ketone body salts leads to a high intake of accompanying minerals, which can lead to additional side effects. The use of mineral-free formulations could improve tolerability. METHODS: In this report, the use of a βHB acid (βHBA) in a patient with MADD is described. The production of D/L-βHBA was carried out using ion exchange chromatography (IEX) and using a precipitation method. During two inpatient treatment intervals, the tolerability as well as clinical and metabolic effects were monitored. D-βHB in serum, blood gas analysis, and standard blood measurements (like minerals) were used as control parameters. RESULTS: Production of D/L-βHBA using the precipitation method was more effective than using IEX. The tube feed solution used had a minimum pH of 3.5. Capillary D-βHB measurements were between 0.1 and 0.4 mmol/L and venous were at 0.1 mmol/L or below. Minerals and serum pH were within the normal range. During application of D/L-βHBA, gastrointestinal discomfort occurred and no clinical improvement was observed. CONCLUSIONS: The use of D/L-βHBA in the therapy of severe MADD could be a good addition to the use of classical ketone body salts. The observed gastrointestinal side effects were of a mild nature and could not be specifically attributed to the D/L-βHBA treatment. In short-term application, no clinical benefit and no substantial increase of D-βHB in serum were noted. No tendency towards acidosis or alkalosis was observed during the entire period of treatment.
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spelling pubmed-66102402019-07-16 Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD Fischer, Tobias Elpers, Christiane Och, Ulrike Fobker, Manfred Marquardt, Thorsten Mol Genet Metab Rep Research Paper OBJECTIVES: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a severe inborn disorder of mitochondrial fatty acid oxidation. The only treatment option for MADD is the use of exogenous ketone bodies, like sodium β-hydroxybutyrate (NaβHB). However, the use of ketone body salts leads to a high intake of accompanying minerals, which can lead to additional side effects. The use of mineral-free formulations could improve tolerability. METHODS: In this report, the use of a βHB acid (βHBA) in a patient with MADD is described. The production of D/L-βHBA was carried out using ion exchange chromatography (IEX) and using a precipitation method. During two inpatient treatment intervals, the tolerability as well as clinical and metabolic effects were monitored. D-βHB in serum, blood gas analysis, and standard blood measurements (like minerals) were used as control parameters. RESULTS: Production of D/L-βHBA using the precipitation method was more effective than using IEX. The tube feed solution used had a minimum pH of 3.5. Capillary D-βHB measurements were between 0.1 and 0.4 mmol/L and venous were at 0.1 mmol/L or below. Minerals and serum pH were within the normal range. During application of D/L-βHBA, gastrointestinal discomfort occurred and no clinical improvement was observed. CONCLUSIONS: The use of D/L-βHBA in the therapy of severe MADD could be a good addition to the use of classical ketone body salts. The observed gastrointestinal side effects were of a mild nature and could not be specifically attributed to the D/L-βHBA treatment. In short-term application, no clinical benefit and no substantial increase of D-βHB in serum were noted. No tendency towards acidosis or alkalosis was observed during the entire period of treatment. Elsevier 2019-06-28 /pmc/articles/PMC6610240/ /pubmed/31312603 http://dx.doi.org/10.1016/j.ymgmr.2019.100491 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Fischer, Tobias
Elpers, Christiane
Och, Ulrike
Fobker, Manfred
Marquardt, Thorsten
Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD
title Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD
title_full Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD
title_fullStr Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD
title_full_unstemmed Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD
title_short Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD
title_sort ketone body therapy with d/l-β-hydroxybutyric acid solution in severe madd
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610240/
https://www.ncbi.nlm.nih.gov/pubmed/31312603
http://dx.doi.org/10.1016/j.ymgmr.2019.100491
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