Observations regarding retinopathy in mitochondrial trifunctional protein deficiencies

Autumn L. Fletcher, Mark E. Pennesi, Cary O. Harding, Richard G. Weleber, Melanie B. Gillingham

Research output: Contribution to journalReview articlepeer-review

51 Scopus citations


Although the retina is thought to primarily rely on glucose for fuel, inherited deficiency of one or more activities of mitochondrial trifunctional protein results in a pigmentary retinopathy leading to vision loss. Many other enzymatic deficiencies in fatty acid oxidation pathways have been described, none of which results in retinal complications. The etiology of retinopathy among patients with defects in trifunctional protein is unknown. Trifunctional protein is a heteroctomer; two genes encode the alpha and beta subunits of TFP respectively, HADHA and HADHB. A common mutation in HADHA, c.1528. G > C, leads to a single amino acid substitution, p. Glu474Gln, and impairs primarily long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity leading to LCHAD deficiency (LCHADD). Other mutations in HADHA or HADHB often lead to significant reduction in all three enzymatic activities and result in trifunctional protein deficiency (TFPD). Despite many similarities in clinical presentation and phenotype, there is growing evidence that they can result in different chronic complications. This review will outline the clinical similarities and differences between LCHADD and TFPD, describe the course of the associated retinopathy, propose a genotype/phenotype correlation with the severity of retinopathy, and discuss the current theories about the etiology of the retinopathy.

Original languageEnglish (US)
Pages (from-to)18-24
Number of pages7
JournalMolecular Genetics and Metabolism
Issue number1
StatePublished - May 2012


  • Fatty acid oxidation
  • Hydroxyacylcarnitines
  • Inborn errors of metabolism
  • Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
  • Mitochondrial trifunctional protein deficiency
  • Retinopathy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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