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

van Rijt, Willemijn J; Jager, Emmalie A; Allersma, Derk P; Aktuğlu Zeybek, A Çiğdem; Bhattacharya, Kaustuv; Debray, François-Guillaume; Ellaway, Carolyn J; Gautschi, Matthias; Geraghty, Michael T; Gil-Ortega, David; Larson, Austin A; Moore, Francesca; Morava, Eva; Morris, Andrew A; Oishi, Kimihiko; Schiff, Manuel; Scholl-Bürgi, Sabine; Tchan, Michel C; Vockley, Jerry; Witters, Peter; ... (2020). Efficacy and safety of D,L-3-hydroxybutyrate (D,L-3-HB) treatment in multiple acyl-CoA dehydrogenase deficiency. Genetics in medicine, 22(5), pp. 908-916. Springer Nature 10.1038/s41436-019-0739-z

[img]
Preview
Text
s41436-019-0739-z.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND).

Download (574kB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders

UniBE Contributor:

Gautschi, Matthias

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1530-0366

Publisher:

Springer Nature

Language:

English

Submitter:

Karen Lidzba

Date Deposited:

29 Jan 2020 10:04

Last Modified:

08 May 2020 01:32

Publisher DOI:

10.1038/s41436-019-0739-z

PubMed ID:

31904027

Uncontrolled Keywords:

D,L-3-hydroxybutyrate treatment fatty acid oxidation inborn error of metabolism ketone bodies multiple acyl-CoA dehydrogenase deficiency

BORIS DOI:

10.7892/boris.138671

URI:

https://boris.unibe.ch/id/eprint/138671

Actions (login required)

Edit item Edit item
Provide Feedback