Observations regarding retinopathy in mitochondrial trifunctional protein deficiencies

Mol Genet Metab. 2012 May;106(1):18-24. doi: 10.1016/j.ymgme.2012.02.015. Epub 2012 Mar 8.

Abstract

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.1528G>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.

Publication types

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

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain* / deficiency
  • Acyl-CoA Dehydrogenase, Long-Chain* / genetics
  • Acyl-CoA Dehydrogenase, Long-Chain* / metabolism
  • Humans
  • Lipid Metabolism, Inborn Errors / genetics
  • Lipid Metabolism, Inborn Errors / metabolism
  • Mitochondria / enzymology
  • Mitochondria / pathology*
  • Mitochondrial Trifunctional Protein
  • Mitochondrial Trifunctional Protein, alpha Subunit
  • Mitochondrial Trifunctional Protein, beta Subunit
  • Multienzyme Complexes* / deficiency
  • Multienzyme Complexes* / genetics
  • Multienzyme Complexes* / metabolism
  • Mutation
  • Phenotype
  • Retina* / enzymology
  • Retina* / pathology
  • Retinal Diseases / genetics
  • Retinal Diseases / metabolism*

Substances

  • Multienzyme Complexes
  • HADHA protein, human
  • Mitochondrial Trifunctional Protein, alpha Subunit
  • Acyl-CoA Dehydrogenase, Long-Chain
  • HADHB protein, human
  • Mitochondrial Trifunctional Protein
  • Mitochondrial Trifunctional Protein, beta Subunit