Characterization of Chorioretinopathy Associated with Mitochondrial Trifunctional Protein Disorders: Long-Term Follow-up of 21 Cases

Ophthalmology. 2016 Oct;123(10):2183-95. doi: 10.1016/j.ophtha.2016.06.048. Epub 2016 Aug 2.


Purpose: To assess long-term effects of genotype on chorioretinopathy severity in patients with mitochondrial trifunctional protein (MTP) disorders.

Design: Retrospective case series.

Participants: Consecutive patients with MTP disorders evaluated at a single center from 1994 through 2015, including 18 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 patients with trifunctional protein deficiency (TFPD).

Methods: Local records from all visits were reviewed. Every participant underwent a complete ophthalmic examination and was evaluated by a metabolic physician and dietitian. Nine patients underwent ancillary funduscopic imaging including optical coherence tomography (OCT) and OCT angiography.

Main outcome measures: The primary outcome measure was best-corrected visual acuity at the final visit. Secondary outcome measures included spherical equivalent refraction, visual fields, electroretinography B-wave amplitudes, and qualitative imaging findings.

Results: Participants were followed up for a median of 5.6 years (range 0.3-20.2 years). The median age of LCHADD participants at initial and final visits was 2.3 and 11.9 years, whereas that for TFPD participants at initial and final visits was 4.7 and 15.5 years, respectively. Four long-term survivors older than 16 years were included (3 with LCHADD and 1 with TFPD). The LCHADD participants demonstrated a steady decline in visual acuity from an average of 0.23 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/34) at baseline to 0.42 logMAR (Snellen equivalent, 20/53) at the final visit, whereas TFPD patients maintained excellent acuity throughout follow-up. Participants with LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in spherical equivalent refraction of 0.24 diopters per year. Visual fields showed sensitivity losses centrally associated with defects on OCT. Multimodal imaging demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by the formation of outer retinal tubulations and choriocapillaris dropout. Electroretinography findings support the more severe clinical profile of LCHADD patients compared with TFPD patients; the function of both rods and cones are attenuated diffusely in LCHADD patients, but are within normal limits for TFPD patients.

Conclusions: Despite improved survival with early diagnosis, medical management, and dietary treatment, participants with the LCHADD subtype of MTP disorder continue to demonstrate visually disabling chorioretinopathy. Multimodal imaging is most consistent with choriocapillaris loss exceeding photoreceptor loss.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Cardiomyopathies / complications*
  • Cardiomyopathies / diagnosis
  • Cardiomyopathies / genetics
  • Child
  • Child, Preschool
  • Choroid Diseases / diagnosis
  • Choroid Diseases / etiology*
  • Choroid Diseases / genetics
  • Electroretinography
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Forecasting*
  • Fundus Oculi
  • Genotype
  • Humans
  • Infant
  • Lipid Metabolism, Inborn Errors / complications*
  • Lipid Metabolism, Inborn Errors / diagnosis
  • Lipid Metabolism, Inborn Errors / genetics
  • Male
  • Mitochondrial Myopathies / complications*
  • Mitochondrial Myopathies / diagnosis
  • Mitochondrial Myopathies / genetics
  • Mitochondrial Trifunctional Protein / deficiency*
  • Mitochondrial Trifunctional Protein / genetics*
  • Mitochondrial Trifunctional Protein / metabolism
  • Nervous System Diseases / complications*
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / genetics
  • Prognosis
  • Retrospective Studies
  • Rhabdomyolysis / complications*
  • Rhabdomyolysis / diagnosis
  • Rhabdomyolysis / genetics
  • Tomography, Optical Coherence
  • Visual Acuity*
  • Visual Fields
  • Young Adult


  • Mitochondrial Trifunctional Protein

Supplementary concepts

  • Trifunctional Protein Deficiency With Myopathy And Neuropathy