June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Indications of mitochondrial dysfunction in Wolfram syndrome.
Author Affiliations & Notes
  • Chiara La Morgia
    IRCCS Institute of Neurological Sciences of Bologna, Neurology Clinic, Bellaria Hospital, Bologna, BO, Italy
    Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, BO, Italy
  • Michele Carbonelli
    IRCCS Institute of Neurological Sciences of Bologna, Neurology Clinic, Bellaria Hospital, Bologna, BO, Italy
  • Leonardo Caporali
    IRCCS Institute of Neurological Sciences of Bologna, Neurology Clinic, Bellaria Hospital, Bologna, BO, Italy
  • Francesca Tagliavini
    IRCCS Institute of Neurological Sciences of Bologna, Neurology Clinic, Bellaria Hospital, Bologna, BO, Italy
  • Giulia Amore
    Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, BO, Italy
    IRCCS Institute of Neurological Sciences of Bologna, Neurology Clinic, Bellaria Hospital, Bologna, BO, Italy
  • federico sadun
    Ospedale San Giovanni Evangelista, Tivoli, Italy
  • Caterina Tonon
    Functional MR Unit - S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
  • Ludovica Gramegna
    Functional MR Unit - S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
  • Raffaele Lodi
    Functional MR Unit - S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
  • Piero Barboni
    IRCCS Institute of Neurological Sciences of Bologna, Neurology Clinic, Bellaria Hospital, Bologna, BO, Italy
  • Rocco Liguori
    IRCCS Institute of Neurological Sciences of Bologna, Neurology Clinic, Bellaria Hospital, Bologna, BO, Italy
    Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, BO, Italy
  • Valerio Carelli
    IRCCS Institute of Neurological Sciences of Bologna, Neurology Clinic, Bellaria Hospital, Bologna, BO, Italy
    Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, BO, Italy
  • Footnotes
    Commercial Relationships   Chiara La Morgia, None; Michele Carbonelli, None; Leonardo Caporali, None; Francesca Tagliavini, None; Giulia Amore, None; federico sadun, None; Caterina Tonon, None; Ludovica Gramegna, None; Raffaele Lodi, None; Piero Barboni, None; Rocco Liguori, None; Valerio Carelli, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5132. doi:
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      Chiara La Morgia, Michele Carbonelli, Leonardo Caporali, Francesca Tagliavini, Giulia Amore, federico sadun, Caterina Tonon, Ludovica Gramegna, Raffaele Lodi, Piero Barboni, Rocco Liguori, Valerio Carelli; Indications of mitochondrial dysfunction in Wolfram syndrome.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5132.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Wolfram type 1 (WFS1) recessive mutations are associated with Wolfram syndrome (WS), defined by early-onset diabetes mellitus and optic atrophy. A longstanding debate concerns the possible mitochondrial dysfunction in WS, apparently resolved by the identification of causative mutations in wolframin, a protein mostly localized on the endoplasmic reticulum. We here explore the possible occurrence of mitochondrial dysfunction in a case-series of WS patients and report clinical, neuroradiological and ophthalmological findings.

Methods : We investigated a cohort of 11 WFS1 adult cases (34.3 ± 13.4 years). Neurophthalmological examination included visual acuity, color vision, pupil, visual field, optical coherence tomography, and fundus picture. In a subgroup of patients we also evaluated lactic acid after standardized
exercise, brain-MRI, muscle and brain MR-spectroscopy (MRS).

Results : Age at onset of visual loss was 10.1 ± 4.1 years. All but one had diabetes mellitus and 7/9 had abnormal lactic acid after exercise. Brain MRI variably demonstrated cortical, brainstem and cerebellar atrophy and white matter changes. Brain 1H-MRS showed lactic acid traces in 2/7. Muscle 31P-MRS was abnormal in 1/6. Visual acuity was 0.19 ± 0.18 with impaired color vision in all cases, and abnormal pupillary response in 7/11. Fundus oculi demonstrated diffuse pallor in 8/11 (more temporal in 3/8) and temporal pallor in 3/11 (Fig 1). Visual fields demonstrated generalized defect in 9/11 and central scotoma in 2/11 (Fig 2). OCT showed diffuse and severe retinal nerve fiber thinning in all cases compared to age-matched controls (p<0.001).

Conclusions : Neurophthalmological phenotype has been poorly characterized in WS. Severe optic atrophy, more evident in the temporal sector concordant with a postmortem study showing a mitochondrial pattern of axonal loss, abnormal lactic acid after exercise and some degree of altered MRS (brain and muscle) all point to a mitochondrial dysfunction in WS.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Examples of fundus pictures in WS. Upper line: temporal pallor; lower line: diffuse pallor of the optic disc.

Examples of fundus pictures in WS. Upper line: temporal pallor; lower line: diffuse pallor of the optic disc.

 

Examples of visual defects in WS. (A) Diffuse defect (B) Central scotoma

Examples of visual defects in WS. (A) Diffuse defect (B) Central scotoma

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