van Rijt, Willemijn JWillemijn Jvan RijtJager, Emmalie AEmmalie AJagerAllersma, Derk PDerk PAllersmaAktuğlu Zeybek, A ÇiğdemA ÇiğdemAktuğlu ZeybekBhattacharya, KaustuvKaustuvBhattacharyaDebray, François-GuillaumeFrançois-GuillaumeDebrayEllaway, Carolyn JCarolyn JEllawayGautschi, MatthiasMatthiasGautschi0000-0003-1358-1759Geraghty, Michael TMichael TGeraghtyGil-Ortega, DavidDavidGil-OrtegaLarson, Austin AAustin ALarsonMoore, FrancescaFrancescaMooreMorava, EvaEvaMoravaMorris, Andrew AAndrew AMorrisOishi, KimihikoKimihikoOishiSchiff, ManuelManuelSchiffScholl-Bürgi, SabineSabineScholl-BürgiTchan, Michel CMichel CTchanVockley, JerryJerryVockleyWitters, PeterPeterWittersWortmann, Saskia BSaskia BWortmannvan Spronsen, FrancjanFrancjanvan SpronsenVan Hove, Johan L KJohan L KVan HoveDerks, Terry G JTerry G JDerks2024-10-282024-10-282020-05https://boris-portal.unibe.ch/handle/20.500.12422/185917PURPOSE 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.enDL-3-hydroxybutyrate treatment fatty acid oxidation inborn error of metabolism ketone bodies multiple acyl-CoA dehydrogenase deficiency600 - Technology::610 - Medicine & healtharticle10.7892/boris.1386713190402710.1038/s41436-019-0739-z