Adult polyglucosan body disease

Adult polyglucosan body disease (APBD) is a rare inherited neurological disorder caused by the accumulation of polyglucosan bodies — abnormal, poorly branched glycogen-like molecules — in the central and peripheral nervous systems, as well as in other tissues. The disease is caused by mutations in the GBE1 gene, which encodes the glycogen branching enzyme. APBD typically manifests in the fifth decade of life or later and primarily affects the nervous system, leading to a combination of upper and lower motor neuron dysfunction, sensory neuropathy, neurogenic bladder, and progressive cognitive impairment. Patients commonly present with progressive difficulty walking due to spastic paraparesis and peripheral neuropathy, urinary urgency or incontinence, and later may develop dementia. APBD is particularly prevalent among individuals of Ashkenazi Jewish descent, in whom a specific founder mutation (p.Tyr329Ser) in the GBE1 gene has been identified, though the disease occurs in other ethnic groups as well. Diagnosis is supported by nerve biopsy showing polyglucosan body inclusions, reduced glycogen branching enzyme activity in leukocytes, and confirmed by molecular genetic testing of GBE1. Brain MRI may show white matter abnormalities. There is currently no cure or disease-modifying treatment for APBD. Management is supportive and symptomatic, focusing on physical therapy to maintain mobility, management of neurogenic bladder (including intermittent catheterization), treatment of spasticity, and cognitive support as needed. Research into potential therapies, including enzyme replacement and gene therapy approaches, is ongoing but remains in early stages.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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