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Multisystem Disorder in Late-Onset Chronic Progressive External Ophthalmoplegia

Published online by Cambridge University Press:  02 December 2014

Gerald Pfeffer
Affiliation:
Division of Neurology, University of British Columbia
Sandra Sirrs
Affiliation:
Division of Endocrinology, University of British Columbia Adult Metabolic Disease Clinic, Vancouver General Hospital, Vancouver, British Columbia, Canada
N. Kevin Wade
Affiliation:
Department of Ophthalmology and Visual Sciences, University of British Columbia
Michelle M. Mezei*
Affiliation:
Division of Neurology, University of British Columbia Adult Metabolic Disease Clinic, Vancouver General Hospital, Vancouver, British Columbia, Canada
*Corresponding
Adult Metabolic Diseases Clinic, 4th Floor, 2775 Laurel St., Vancouver, British Columbia, V5Z 1M9, Canada
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Abstract:

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Introduction:

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial syndrome on a disease spectrum with Kearns-Sayre syndrome (KSS). Clinical presentation is variable and our experience suggested that phenotypic differences exist in CPEO with onset after age 20.

Methods:

This descriptive study is a retrospective chart review of 40 patients with late-onset CPEO. Clinical features, laboratory and neurophysiology results were reviewed.

Results:

Multisystem dysfunction was very common in this series. Gastrointestinal dysfunction was more common than expected (60%) as was migraine headache (40%). Clinical characteristics on the KSS disease spectrum were uncommon in this series with only 2.5% having pigmentary retinopathy, 5% with cardiac conduction abnormality, and 22.5% having endocrinopathy (most often thyroid dysfunction rather than diabetes). Neurophysiology abnormalities included length-dependent axonal polyneuropathy in 44% (sometimes subclinical) and myopathic EMG changes in 26%. Exposure to sources of acquired mitochondrial toxicity including cigarette use and hepatitis C infection were more common than expected in this series.

Discussion:

Phenotype was different in this late-onset series compared with previous reports in CPEO patients. In this series of late-onset patients, multi-organ dysfunction was more common than previously reported in CPEO, and some classical mitochondrial manifestations, such as pigmentary retinopathy were rare. We suggest that acquired mitochondrial toxicity may have a role in the pathogenesis of adult-onset CPEO.

Résumé:

Résumé: Contexte:

L'ophtalmoplégie externe progressive chronique (OEPC) est un syndrome mitochondrial qui se situe dans le spectre de maladies dont fait partie le syndrome de Kearns-Sayre (SKS). Sa présentation clinique est variable et, selon notre expérience, nous croyons qu'il existe des différences phénotypiques dans l'OEPC qui commence après l'âge de 20 ans.

Méthodes:

Il s'agit d'une étude descriptive de 40 patients atteints d'OEPC à début tardif dont nous avons révisé rétrospectivement les dossiers pour en tirer les observations cliniques, les données de laboratoire et les résultats d'études neurophysiologiques.

Résultats:

La dysfonction multisystémique était très fréquente chez ces patients. La dysfonction gastrointestinale (60%) et la migraine (40%) étaient plus fréquentes qu‘attendu. Les caractéristiques cliniques du spectre du SKS étaient rares dans cette série de patients, seulement 2,5% étant porteurs d'une rétinopathie pigmentaire, 5% d'anomalies de conduction cardiaque et 22,5% d'endocrinopathies (la plupart du temps une dysfonction thyroïdienne plutôt qu'un diabète). Parmi les anomalies neurophysiologiques, nous avons retrouvé une polyneuropathie axonale longueur-dépendante chez 44% (parfois subclinique) et des changements de type myopathique à l'EMG chez 26%. Une exposition à des sources de toxicité mitochondriale acquise dont le tabagisme et l'infection par le virus de l'hépatite C était plus fréquente qu'attendu dans cette série de cas.

Discussion:

Le phénotype était différent chez nos cas à début tardif comparé à celui décrit dans les études publiées antérieurement. Chez nos patients atteints d'OEPC à début tardif, une dysfonction multisystémique était plus fréquente que chez les cas publiés antérieurement et certaines manifestations mitochondriales classiques telle une rétinopathie pigmentaire étaient rares. Nous proposons qu'une toxicité mitochondriale acquise puisse jouer un rôle dans la pathogenèse de l'OEPC débutant à l'âge adulte.

Type
Original Article
Copyright
Copyright © Canadian Neurological Sciences Federation 2011

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