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 - 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
SN - 1098-3600
VL - 22
SP - 908
EP - 916
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 5
ER -