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Fischer T, Elpers C, Och U, et al. Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD. Mol Genet Metab Rep. 2019;20:100491doi: 10.1016/j.ymgmr.2019.100491.
Fischer, T., Elpers, C., Och, U., Fobker, M., & Marquardt, T. (2019). Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD. Molecular genetics and metabolism reports, 20100491. https://doi.org/10.1016/j.ymgmr.2019.100491
Fischer, Tobias, et al. "Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD." Molecular genetics and metabolism reports vol. 20 (2019): 100491. doi: https://doi.org/10.1016/j.ymgmr.2019.100491
Fischer T, Elpers C, Och U, Fobker M, Marquardt T. Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD. Mol Genet Metab Rep. 2019 Jun 28;20:100491. doi: 10.1016/j.ymgmr.2019.100491. eCollection 2019 Sep. PMID: 31312603; PMCID: PMC6610240.
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Mol Genet Metab Rep. 2019 Jun 28;20:100491. doi: 10.1016/j.ymgmr.2019.100491. eCollection 2019 Sep.

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

Molecular genetics and metabolism reports

Tobias Fischer, Christiane Elpers, Ulrike Och, Manfred Fobker, Thorsten Marquardt

Affiliations

  1. University Hospital Muenster, Department of Pediatrics, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.
  2. University Hospital Muenster, Center of laboratory medicine, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.

PMID: 31312603 PMCID: PMC6610240 DOI: 10.1016/j.ymgmr.2019.100491

Abstract

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.

Keywords: Ketone bodies; Ketone body salts; Ketone body therapy; MADD; Metabolic disease; β-Hydroxybutyric acid

Conflict of interest statement

None.

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