title: Frequent misdiagnosis of adult polyglucosan body disease.
abstract: Adult polyglucosan body disease (APBD) is a rare glycogenosis manifesting progressive spastic paraparesis, sensorimotor polyneuropathy and neurogenic bladder. Misdiagnosis of APBD may lead to unnecessary investigations and to potentially harmful therapeutic interventions. To examine the frequency of misdiagnosis of APBD, we retrospectively reviewed the clinical data of 30 patients diagnosed between 1991 and 2013. Diagnosis was based on the combination of typical clinical and imaging findings, reduced glycogen branching enzyme activity, and the presence of p.Y326S GBE1 mutation. Initial symptoms started in the 5th-6th decade with bladder dysfunction (47 %), gait problems (33 %) or both. Diagnosis of APBD was delayed by 6.8 (±4.8) years. Consistent signs at diagnosis were spasticity in the legs (93 %), decreased or absent ankle reflexes (100 %), bilateral extensor plantar response (100 %) and distal sensory deficit (80 %). Nerve conduction study showed invariable sensorimotor polyneuropathy, and MRI demonstrated cervical spinal cord atrophy (100 %) and leukoencephalopathy (97 %). All 30 patients were initially misdiagnosed. Common misdiagnoses included cerebral small vessel disease (27 %), multiple sclerosis (17 %), amyotrophic lateral sclerosis (17 %) and peripheral neuropathies (20 %). Consequently, 27 % received inappropriate therapy. In addition, lower urinary tract symptoms in 60 % of men were attributed solely to prostatic disorders but did not respond to medical treatment or prostatectomy. These findings suggest that despite limited clinical variability, APBD is invariably misdiagnosed and patients are often mistreated. Physicians' unfamiliarity with the typical clinical and imaging features of APBD appears as the main reason for misdiagnosis.
authors.affiliation: Department of Neurology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel.|Sacker Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hellmann
authors.affiliation: Department of Neurology and the Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel.
authors.forename: Or
authors.initials: O
authors.lastname: Kakhlon
authors.affiliation: Department of Urology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ezekiel H
authors.initials: EH
authors.lastname: Landau
authors.affiliation: Department of Neurology, Wolfson Medical Center, Holon, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Sadeh
authors.affiliation: Sacker Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Neurology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Giladi
authors.affiliation: Department of Neurology, Rambam Health Care Campus, Technion Faculty of Medicine, Haifa, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Schlesinger
authors.affiliation: Maccabi Health Services, Tel Aviv, Israel.
authors.forename: Daphne
authors.initials: D
authors.lastname: Kidron
authors.affiliation: Department of Neurology and the Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Abramsky
authors.affiliation: Department of Neurology and the Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel.
authors.forename: Avinoam
authors.initials: A
authors.lastname: Reches
authors.affiliation: Department of Neurology and the Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
authors.affiliation: Department of Neurology, Assaf Harofeh Medical Center, Rishon Le Zion, Israel.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Rabey
authors.affiliation: Sacker Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Neurology, The Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Joab
authors.initials: J
authors.lastname: Chapman
authors.affiliation: Department of Neurology and the Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel.
authors.forename: Hanna
authors.initials: H
authors.lastname: Rosenmann
authors.affiliation: Department of Neurology and the Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel.
authors.forename: Aya
authors.initials: A
authors.lastname: Gal
authors.affiliation: Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Moshe Gomori
authors.affiliation: Department of Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Vardiella
authors.initials: V
authors.lastname: Meiner
authors.affiliation: Department of Neurology and the Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel. alos@hadassah.org.il.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lossos
mesh_terms: D000328:Adult; D000368:Aged; D057210:Delayed Diagnosis; D003951:Diagnostic Errors; D005260:Female; D006008:Glycogen Storage Disease / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000628:therapy; D012189:Retrospective Studies
keywords: Adult polyglucosan body disease; GBE1 gene; Glycogen branching enzyme; Spastic paraparesis