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Frequent misdiagnosis of adult polyglucosan body disease


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.

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Dr. Kakhlon is supported in part by the Adult Polyglucosan Body Disease Research Foundation research grant for studies in APBD and in part by the AFM (Association Française contre les Myopathies)-Telethon Grant for studies in neuropolyglucosanoses. Dr. Giladi incumbents the Sieratzki Chair in Neurology.

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Correspondence to Alexander Lossos.

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The authors report no conflicts of interest. Funders of Dr. Kakhlon’s research had no role in the design and conduct of the study, collection and interpretation of the data, and preparation or approval of the manuscript.

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The study was approved by the Hadassah-Hebrew University Medical Center Institutional Review Board, and patients gave their informed consent prior to their inclusion in the study.

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Hellmann, M.A., Kakhlon, O., Landau, E.H. et al. Frequent misdiagnosis of adult polyglucosan body disease. J Neurol 262, 2346–2351 (2015).

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  • Adult polyglucosan body disease
  • Glycogen branching enzyme
  • GBE1 gene
  • Spastic paraparesis