Evaluation of earlier versus later dietary management in long-chain 3-hydroxyacyl-CoA dehydrogenase or mitochondrial trifunctional protein deficiency: a systematic review

Hannah Fraser, Julia Geppert, Rebecca Johnson, Samantha Johnson, Martin Connock, Aileen Clarke, Sian Taylor-Phillips, Christopher Stinton

Research output: Contribution to journalReview articlepeer-review

16 Citations (Scopus)
31 Downloads (Pure)


Background: Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid β-oxidation disorders. Without dietary management the conditions are life-threatening. We conducted a systematic review to investigate whether pre-symptomatic dietary management following newborn screening provides better outcomes than treatment following symptomatic detection. Methods: We searched Web of Science, Medline, Pre-Medline, Embase and the Cochrane Library up to 23rd April 2018. Two reviewers independently screened titles, abstracts and full texts for eligibility and quality appraised the studies. Data extraction was performed by one reviewer and checked by another. Results: We included 13 articles out of 7483 unique records. The 13 articles reported on 11 patient groups, including 174 people with LCHAD deficiency, 18 people with MTP deficiency and 12 people with undifferentiated LCHAD/MTP deficiency. Study quality was moderate to weak in all studies. Included studies suggested fewer heart and liver problems in screen-detected patients, but inconsistent results for mortality. Follow up analyses compared long-term outcomes of (1) pre-symptomatically versus symptomatically treated patients, (2) screened versus unscreened patients, and (3) asymptomatic screen-detected, symptomatic screen-detected, and clinically diagnosed patients in each study. For follow up analyses 1 and 2, we found few statistically significant differences in the long-term outcomes. For follow up analysis 3 we found a significant difference for only one comparison, in the incidence of cardiomyopathy between the three groups. Conclusions: There is some evidence that dietary management following screen-detection might be associated with a lower incidence of some LCHAD and MTP deficiency-related complications. However, the evidence base is limited by small study sizes, quality issues and risk of confounding. An internationally collaborative research effort is needed to fully examine the risks and the benefits to pre-emptive dietary management with particular attention paid to disease severity and treatment group.

Original languageEnglish
Article number258
Number of pages18
JournalOrphanet Journal of Rare Diseases
Publication statusPublished - 15 Nov 2019

Bibliographical note

This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
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  • Systematic Review
  • Rare disease
  • long-chain 3-hydroxyacyl-CoA dehydrogenase or mitochondrial trifunctional protein deficiency
  • Inborn errors of metabolism
  • Long-chain 3-hydroxyacyl-CoA dehydrogenase
  • Long-term outcomes
  • Newborn screening
  • Systematic review
  • Mitochondrial trifunctional protein deficiency

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)


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