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Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings

Authors

  • Fanny Mochel MD, PhD,

    Corresponding author
    1. French Institute of Health and Medical Research, UMR S975, Brain and Spine Institute, Salpêtrière Hospital, Paris, France
    2. AP-HP, Department of Genetic, Salpêtrière Hospital, Paris, France
    3. Neurometabolic Unit, Salpêtrière Hospital, Paris, France
    4. University Pierre and Marie Curie, Paris, France
    • Brain and Spine Institute, INSERM UMR S975, Hôpital de La Salpêtrière, 75013 Paris, France
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  • Raphael Schiffmann MD,

    1. Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX
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  • Marjan E. Steenweg MD,

    1. VU University Medical Center, Department of Child Neurology, Center for Childhood White Matter Disorders, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands
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  • Hasan O. Akman PhD,

    1. Columbia University Medical Center, Department of Neurology, New York, NY
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  • Mary Wallace RD,

    1. Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX
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  • Frédéric Sedel MD, PhD,

    1. French Institute of Health and Medical Research, UMR S975, Brain and Spine Institute, Salpêtrière Hospital, Paris, France
    2. Neurometabolic Unit, Salpêtrière Hospital, Paris, France
    3. AP-HP, Department of Neurology, Salpêtrière Hospital, Paris, France
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  • Pascal Laforêt MD,

    1. Neurometabolic Unit, Salpêtrière Hospital, Paris, France
    2. AP-HP, East Paris Neuromuscular Pathology Referral Center, Salpêtrière Hospital, Paris, France
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  • Richard Levy MD, PhD,

    1. University Pierre and Marie Curie, Paris, France
    2. French Institute of Health and Medical Research U610, Cognition, Neuroimaging, and Brain Diseases, Paris, France
    3. AP-HP, Department of Neurology, Saint-Antoine Hospital, Paris, France
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  • J. Michael Powers MD,

    1. Affiliated Neurologists Ltd, Phoenix, AZ
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  • Sophie Demeret MD,

    1. AP-HP, Department of Neurology, Salpêtrière Hospital, Paris, France
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  • Thierry Maisonobe MD,

    1. AP-HP, Department of Neurophysiology and Neuropathology, Salpêtrière Hospital, Paris, France
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  • Roseline Froissart PhD,

    1. Laboratory of Inborn Errors of Metabolism, Civil Hospices of Lyon, Bron, France
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  • Bruno Barcelos Da Nobrega MD,

    1. Department of Radiology, São Camilo Hospital, São Paulo, Brazil
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  • Brent L. Fogel MD, PhD,

    1. Department of Neurology, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA
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  • Marvin R. Natowicz MD, PhD,

    1. Pathology and Laboratory Medicine Institute and Institutes of Genomic Medicine, Neurology, and Pediatrics, Cleveland Clinic, Cleveland, OH
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  • Catherine Lubetzki MD, PhD,

    1. French Institute of Health and Medical Research, UMR S975, Brain and Spine Institute, Salpêtrière Hospital, Paris, France
    2. University Pierre and Marie Curie, Paris, France
    3. AP-HP, Department of Neurology, Salpêtrière Hospital, Paris, France
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  • Alexandra Durr MD, PhD,

    1. Affiliated Neurologists Ltd, Phoenix, AZ
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  • Alexis Brice MD,

    1. French Institute of Health and Medical Research, UMR S975, Brain and Spine Institute, Salpêtrière Hospital, Paris, France
    2. AP-HP, Department of Genetic, Salpêtrière Hospital, Paris, France
    3. University Pierre and Marie Curie, Paris, France
    4. AP-HP, Department of Neurology, Salpêtrière Hospital, Paris, France
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  • Hanna Rosenmann PhD,

    1. Hadassah-Hebrew University Medical Center, Department of Neurology, Jerusalem, Israel
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  • Varda Barash PhD,

    1. Hadassah-Hebrew University Medical Center, Department of Biochemistry, Jerusalem, Israel
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  • Or Kakhlon PhD,

    1. Hadassah-Hebrew University Medical Center, Department of Neurology, Jerusalem, Israel
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  • J. Moshe Gomori MD,

    1. Hadassah-Hebrew University Medical Center, Department of Radiology, Jerusalem, Israel
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  • Marjo S. van der Knaap MD, PhD,

    1. VU University Medical Center, Department of Child Neurology, Center for Childhood White Matter Disorders, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands
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  • Alexander Lossos MD

    1. Hadassah-Hebrew University Medical Center, Department of Neurology, Jerusalem, Israel
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Abstract

Objective:

Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder, progressive spastic gait, and peripheral neuropathy. Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency. To improve clinical diagnosis and enable future evaluation of therapeutic strategies, we conducted a multinational study of the natural history and imaging features of APBD.

Methods:

We gathered clinical, biochemical, and molecular findings in 50 APBD patients with GBE deficiency from Israel, the United States, France, and the Netherlands. Brain and spine magnetic resonance images were reviewed in 44 patients.

Results:

The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%). The median age was 51 years for the onset of neurogenic bladder symptoms, 63 years for wheelchair dependence, and 70 years for death. As the disease progressed, mild cognitive decline may have affected up to half of the patients. Neuroimaging showed hyperintense white matter abnormalities on T2 and fluid attenuated inversion recovery sequences predominantly in the periventricular regions, the posterior limb of the internal capsule, the external capsule, and the pyramidal tracts and medial lemniscus of the pons and medulla. Atrophy of the medulla and spine was universal. p.Y329S was the most common GBE1 mutation, present as a single heterozygous (28%) or homozygous (48%) mutation.

Interpretation:

APBD with GBE deficiency, with occasional exceptions, is a clinically homogenous disorder that should be suspected in patients with adult onset leukodystrophy or spastic paraplegia with early onset of urinary symptoms and spinal atrophy. ANN NEUROL 2012;72:433–441.

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