Publication

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

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., Witters, P., Wortmann, S. B., van Spronsen, F., Van Hove, J. L. K. & Derks, T. G. J., 6-Jan-2020, In : Genetics in Medicine. 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • 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 Witters
  • Saskia B Wortmann
  • Francjan van Spronsen
  • Johan L K Van Hove
  • Terry G J Derks

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
Number of pages9
JournalGenetics in Medicine
Publication statusPublished - 6-Jan-2020

    Keywords

  • D,L-3-hydroxybutyrate treatment, fatty acid oxidation, inborn error of metabolism, ketone bodies, multiple acyl-CoA dehydrogenase deficiency, BETA-HYDROXYBUTYRATE, KETONE-BODIES, GLUCOSE-METABOLISM

ID: 112065365