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

3-Hydroxybutyric Acid Acyl-CoA Dehydrogenase / genetics Cardiomyopathies Humans Infant Multiple Acyl Coenzyme A Dehydrogenase Deficiency / drug therapy Retrospective Studies
D,L-3-hydroxybutyrate treatment fatty acid oxidation inborn error of metabolism ketone bodies multiple acyl-CoA dehydrogenase deficiency

Journal

Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831

Informations de publication

Date de publication:
05 2020
Historique:
received: 19 08 2019
accepted: 18 12 2019
pubmed: 7 1 2020
medline: 28 4 2021
entrez: 7 1 2020
Statut: ppublish

Résumé

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. 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. 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%). 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.

Identifiants

DOI: 10.1038/s41436-019-0739-z PMID: 31904027 PMC: PMC7200590
pubmed: 31904027
doi: 10.1038/s41436-019-0739-z
pii: S1098-3600(21)00853-4
pmc: PMC7200590
doi:

Substances chimiques

Acyl-CoA Dehydrogenase EC 1.3.8.7
3-Hydroxybutyric Acid TZP1275679

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

908-916

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK078775
Pays : United States
Organisme : NIH HHS
ID : Grant R01-DK78755
Pays : United States

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Auteurs

Willemijn J van Rijt (WJ)

Section of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.

Emmalie A Jager (EA)

Section of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.

Derk P Allersma (DP)

Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

A Çiğdem Aktuğlu Zeybek (AÇ)

Division of Nutrition and Metabolism, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Kaustuv Bhattacharya (K)

Genetic Metabolic Disorders Service, Sydney Children's Hospital Network, Disciplines of Genetic Medicine and Child and Adolescent Health, University of Sydney, Sydney, Australia.

François-Guillaume Debray (FG)

Department of Medical Genetics, CHU of Liège, Liège, Belgium.

Carolyn J Ellaway (CJ)

Genetic Metabolic Disorders Service, Sydney Children's Hospital Network, Disciplines of Genetic Medicine and Child and Adolescent Health, University of Sydney, Sydney, Australia.

Matthias Gautschi (M)

University Hospital Bern, Department of Pediatric Endocrinology, Diabetology and Metabolism and University Institute of Clinical Chemistry, Inselspital, University of Bern, Bern, Switzerland.

Michael T Geraghty (MT)

Division of Metabolics and Newborn Screening, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.

David Gil-Ortega (D)

Department of Pediatric Gastroenterology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.

Austin A Larson (AA)

Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Aurora, CO, USA.

Francesca Moore (F)

Biochemical Genetics Laboratory, The Children's Hospital at Westmead, Sydney, Australia.

Eva Morava (E)

Center of Individualized Medicine, Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Metabolic Disease Center, University Hospitals Leuven, Leuven, Belgium.

Andrew A Morris (AA)

Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, United Kingdom.
Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.

Kimihiko Oishi (K)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Manuel Schiff (M)

Reference Centre for Inborn Errors of Metabolism, Robert Debré Univ. Hospital, APHP, INSERM U1141 and Paris Diderot University, Paris, France.

Sabine Scholl-Bürgi (S)

Department of Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Innsbruck, Austria.

Michel C Tchan (MC)

Westmead Hospital, University of Sydney, Sydney, Australia.

Jerry Vockley (J)

Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.

Peter Witters (P)

Metabolic Disease Center, University Hospitals Leuven, Leuven, Belgium.

Saskia B Wortmann (SB)

University Childrens Hospital, Paracelcus Medical University (PMU), Salzburg, Austria.
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
Institute of Human Genetics, Technische Universität München, Munich, Germany.

Francjan van Spronsen (F)

Section of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.

Johan L K Van Hove (JLK)

Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Aurora, CO, USA.

Terry G J Derks (TGJ)

Section of Metabolic Diseases, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen, The Netherlands. t.g.j.derks@umcg.nl.
ORCID: 0000-0002-7259-1095

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Classifications MeSH

questionsmedicales.fr › Lipides › Acides gras › Acides gras volatils › Butyrates › Hydroxy-butyrates › Acide 3-hydroxy-butyrique › Efficacy and safety of D,L-3-hydroxybutyrate...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Flavoprotéines › Acyl-CoA dehydrogenase › Efficacy and safety of D,L-3-hydroxybutyrate...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Cardiomyopathies › Efficacy and safety of D,L-3-hydroxybutyrate...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Efficacy and safety of D,L-3-hydroxybutyrate...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Efficacy and safety of D,L-3-hydroxybutyrate...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Maladies mitochondriales › Déficit multiple en acyl CoA déshydrogénase › Efficacy and safety of D,L-3-hydroxybutyrate...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Efficacy and safety of D,L-3-hydroxybutyrate...