TY - JOUR
T1 - Efficacy and safety of D,L-3-hydroxybutyrate (D,L-3-HB) treatment in multiple acyl-CoA dehydrogenase deficiency
AU - van Rijt, Willemijn J.
AU - Jager, Emmalie A.
AU - Allersma, Derk P.
AU - Aktuğlu Zeybek, A. Çiğdem
AU - Bhattacharya, Kaustuv
AU - Debray, François Guillaume
AU - Ellaway, Carolyn J.
AU - Gautschi, Matthias
AU - Geraghty, Michael T.
AU - Gil-Ortega, David
AU - Larson, Austin A.
AU - Moore, Francesca
AU - Morava, Eva
AU - Morris, Andrew A.
AU - Oishi, Kimihiko
AU - Schiff, Manuel
AU - Scholl-Bürgi, Sabine
AU - Tchan, Michel C.
AU - Vockley, Jerry
AU - Witters, Peter
AU - Wortmann, Saskia B.
AU - van Spronsen, Francjan
AU - Van Hove, Johan L.K.
AU - Derks, Terry G.J.
N1 - Funding Information:
The authors thank Katinka A.M. Mulder, legal advisor—research contracts, for her contribution to the realization of the consortium agreement. Pharmaceutical industries did not play any role in this study. The MD/PhD scholarships of W.J.v.R. and E.A.J. are funded by the Junior Scientific Masterclass from the University of Groningen, University Medical Center Groningen (MD/PhD 15–30, MD/PhD 18–55, respectively). J.V. is supported in part by National Institutes of Health (NIH) grant R01-DK78755. The sources of funding had no involvement in the study design; data collection, analysis, and interpretation; reporting of the results; or in the decision to submit the paper for publication.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - D,L-3-hydroxybutyrate treatment
KW - fatty acid oxidation
KW - inborn error of metabolism
KW - ketone bodies
KW - multiple acyl-CoA dehydrogenase deficiency
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U2 - 10.1038/s41436-019-0739-z
DO - 10.1038/s41436-019-0739-z
M3 - Article
C2 - 31904027
AN - SCOPUS:85077628935
VL - 22
SP - 908
EP - 916
JO - Genetics in Medicine
JF - Genetics in Medicine
SN - 1098-3600
IS - 5
ER -