Efficacy and safety of D,L-3-hydroxybutyrate (D,L-3-HB) treatment in multiple acyl-CoA dehydrogenase deficiencyvan 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 journal › Article › Academic › peer-review
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.
|Number of pages||9|
|Journal||Genetics in Medicine|
|Publication status||Published - 6-Jan-2020|
- 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