Efficacy and safety of D,L-3-hydroxybutyrate (D,L-3-HB) treatment in multiple acyl-CoA dehydrogenase deficiency

Willemijn J. van Rijt, Emmalie A. Jager, Derk P. Allersma, A. Çiğdem Aktuğlu Zeybek, Kaustuv Bhattacharya, François Guillaume Debray, Carolyn J. Ellaway, Matthias Gautschi, Michael T. Geraghty, David Gil-Ortega, Austin A. Larson, Francesca Moore, Eva Morava, Andrew A. Morris, Kimihiko Oishi, Manuel Schiff, Sabine Scholl-Bürgi, Michel C. Tchan, Jerry Vockley, Peter WittersSaskia B. Wortmann, Francjan van Spronsen, Johan L.K. Van Hove, Terry G.J. Derks

Research output: Contribution to journalArticle

Abstract

Purpose: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a life-threatening, ultrarare inborn error of metabolism. Case reports described successful D,L-3-hydroxybutyrate (D,L-3-HB) treatment in severely affected MADD patients, but systematic data on efficacy and safety is lacking. Methods: A systematic literature review and an international, retrospective cohort study on clinical presentation, D,L-3-HB treatment method, and outcome in MADD(-like) patients. Results: Our study summarizes 23 MADD(-like) patients, including 14 new cases. Median age at clinical onset was two months (interquartile range [IQR]: 8 months). Median age at starting D,L-3-HB was seven months (IQR: 4.5 years). D,L-3-HB doses ranged between 100 and 2600 mg/kg/day. Clinical improvement was reported in 16 patients (70%) for cardiomyopathy, leukodystrophy, liver symptoms, muscle symptoms, and/or respiratory failure. D,L-3-HB appeared not effective for neuropathy. Survival appeared longer upon D,L-3-HB compared with historical controls. Median time until first clinical improvement was one month, and ranged up to six months. Reported side effects included abdominal pain, constipation, dehydration, diarrhea, and vomiting/nausea. Median D,L-3-HB treatment duration was two years (IQR: 6 years). D,L-3-HB treatment was discontinued in 12 patients (52%). Conclusion: The strength of the current study is the international pooling of data demonstrating that D,L-3-HB treatment can be effective and safe in MADD(-like) patients.

Original languageEnglish (US)
Pages (from-to)908-916
Number of pages9
JournalGenetics in Medicine
Volume22
Issue number5
DOIs
StatePublished - May 1 2020

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Keywords

  • D,L-3-hydroxybutyrate treatment
  • fatty acid oxidation
  • inborn error of metabolism
  • ketone bodies
  • multiple acyl-CoA dehydrogenase deficiency

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

van Rijt, W. J., Jager, E. A., Allersma, D. P., Aktuğlu Zeybek, A. Ç., Bhattacharya, K., Debray, F. G., Ellaway, C. J., Gautschi, M., Geraghty, M. T., Gil-Ortega, D., Larson, A. A., Moore, F., Morava, E., Morris, A. A., Oishi, K., Schiff, M., Scholl-Bürgi, S., Tchan, M. C., Vockley, J., ... Derks, T. G. J. (2020). Efficacy and safety of D,L-3-hydroxybutyrate (D,L-3-HB) treatment in multiple acyl-CoA dehydrogenase deficiency. Genetics in Medicine, 22(5), 908-916. https://doi.org/10.1038/s41436-019-0739-z