Adult polyglucosan body disease: clinical and histological heterogeneity of a large Italian family.
Adult Polyglucosan Body Disease (APBD) is a rare inherited leukodystrophy associated with axonal polyneuropathy, mainly reported in persons of Ashkenazi-Jewish descent. We describe three Italian siblings at disease onset, presenting in their fifties with a combination of pyramidal and ataxic signs, mild demyelinating neuropathy on neurophysiological investigation (1/3 cases) and transient symptoms (1/3). A leucoencephalopathy with infratentorial lesions without enhancement and medullary/spine atrophy was demonstrated on brain/spine MRI (3/3). Muscle biopsy was normal in 2/3; both muscle and nerve biopsy showed polyglucosan bodies in the sibling with polyneuropathy. This indicated a need for GBE1 sequencing, which revealed a novel missense mutation (c.1064G>A; p.Arg355His) and one previously described (c.1604A>G; p.Tyr535Cys) in all siblings. We highlight that peripheral neuropathy, deemed as disease hallmark, may be missing and that transient symptoms are confirmed as early disease manifestations. The pattern of damage at neuro-imaging described recurs irrespective of clinical presentation, constituting a unifying diagnostic clue.
Neuromuscular Unit, Department of Neuroscience, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. Electronic address: irene.colombo@unimi.it.
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Colombo
Dino Ferrari Centre, Department of Pathophysiology and Transplantation Neuroscience Section (DEPT), Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Pagliarani
Neuromuscular Unit, Department of Neuroscience, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Testolin
Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences, Foundation IRCCS Neurological Institute "C Besta", Milan, Italy.
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Salsano
Neuromuscular Unit, Department of Neuroscience, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Napoli
Dino Ferrari Centre, Department of Pathophysiology and Transplantation Neuroscience Section (DEPT), Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Bordoni
Dino Ferrari Centre, Department of Pathophysiology and Transplantation Neuroscience Section (DEPT), Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Salani
Department of Neurology, Ospedale Maggiore, Crema, Italy.
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D'Adda
Neuromuscular Disorders and Neuroimmunology Dept., Department of Clinical Neurosciences, Foundation IRCCS Neurological Institute "C Besta", Milan, Italy.
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Morandi
Unit of Neuroradiology, Department of Diagnostic and Applied Technology, Foundation IRCCS Neurological Institute "C Besta", Milan, Italy.
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Farina
Dino Ferrari Centre, Department of Pathophysiology and Transplantation Neuroscience Section (DEPT), Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Magri
Department of Neurology, Ospedale Maggiore, Lodi, Italy.
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Riva
Department of Neurology, Ospedale Maggiore, Crema, Italy.
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Prelle
Neuromuscular Unit, Department of Neuroscience, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Sciacco
Dino Ferrari Centre, Department of Pathophysiology and Transplantation Neuroscience Section (DEPT), Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Comi
Neuromuscular Unit, Department of Neuroscience, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Moggio
D005190:Family; D005260:Female; D006008:Glycogen Storage Disease / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000473:pathology; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D009431:Neural Conduction; D010375:Pedigree; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology; D044465:White People
1,4-Alpha-glucan branching enzyme; Adult Polyglucosan Body Disease; GBE1; Leukodystrophy