Efficacy and safety of D,L-3-hydroxybutyrate (D,L-3-HB) treatment in multiple acyl-CoA dehydrogenase deficiency

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Van Rijt W. J., Jager E. A., Allersma D. P., Aktuğlu Zeybek A. Ç., Bhattacharya K., Debray F., ...Daha Fazla

GENETICS IN MEDICINE, cilt.22, sa.5, ss.908-916, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Sayı: 5
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1038/s41436-019-0739-z
  • Dergi Adı: GENETICS IN MEDICINE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED)
  • Sayfa Sayıları: ss.908-916
  • Anahtar Kelimeler: 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
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

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.