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*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

25 Citaten (Scopus)
137 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)908-916
Aantal pagina's9
TijdschriftGenetics in Medicine
Volume22
Nummer van het tijdschrift5
DOI's
StatusPublished - 6-jan.-2020

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