Adult polyglucosan body disease (ORPHA:206583)
A glycogen storage disease of adults characterized by progressive upper and lower motor neuron dysfunction, progressive neurogenic bladder and cognitive difficulties that can lead to dementia.
Epidemiology
The prevalence is unknown. More than 50 cases have been described to date in Ashkenazi (in most cases) and non-Ashkenazi Jewish individuals.
Clinical description
APBD presents after the age of 40, with urinary incontinence (indicative of neurogenic bladder) often being the first manifestation. Progressive spasticity and weakness are also present due to upper and lower motor neuron involvement and patients have difficulty walking. Severity of gait difficulties varies between patients with some requiring a wheelchair at an advanced disease stage. Sensory loss in the distal lower extremities occurs in most individuals and can lead to foot injuries. Cognitive difficulties (such as problems with executive functioning) can be mild but in some cases can lead to dementia.
Etiology
APBD is caused by a mutation in the GBE1 gene, encoding the glucan (1, 4-alpha-) branching enzyme 1 (GBE). Without this enzyme, glycogen is not synthesized properly, regulation of glycogen synthase is dysfunctional and deposition of amylopectin-like polyglucosan bodies in neural tissue occurs. Other mutations in this gene are responsible for a more severe and earlier onset form of the disease known as glycogen storage disease type IV (see this term).
Diagnostic methods
Diagnosis is based on the presence of clinical manifestations of the disease along with the characteristic laboratory findings. Typically, magnetic resonance imaging (MRI) demonstrates cerebral white matter changes in the subcortical and periventricular areas, the posterior limb of the internal capsule and in the brainstem. Cerebral, cerebellar and spinal cord atrophy may also be seen at various stages of the disease. Reduced GBE activity is observed in cultured skin fibroblasts and peripheral blood lymphocytes of patients with APBD and sural nerve biopsy shows the presence of polyglucosan bodies in the nerve. Genetic testing is essential for the diagnosis and makes nerve biopsy unnecessary.
Differential diagnosis
The motor neuron dysfunction seen in APBD may be similar to that seen in amyotrophic lateral sclerosis (see this term). Primary urologic dysfunction, multiple sclerosis and Alzheimer's disease should also be considered, as well as other causes of adult onset myeloneuropathy and leukoencephalopathy.
Antenatal diagnosis
Antenatal diagnosis can be performed but is rarely done as the disease has an adult onset.
Genetic counseling
APBD is inherited autosomal recessively and genetic counseling can be given to those with the GBE1 gene mutations in the family. Pre-symptomatic testing can be performed if considered essential for genetic counseling.
Management and treatment
Treatment requires a multidisciplinary team including specialists in physical medicine rehabilitation, psychology and urology. Urologic management may require antispasmodic bladder medications as well as an indwelling or an in-and-out bladder catheter. Ambulation aids such as canes, walkers and wheelchairs may be needed depending on the severity of gait dysfunction in order to move around safely. A neuropsychometric analysis can identify any cognitive impairment and appropriate cognitive aids and behavioural modification can be given. Follow up is needed to monitor bladder function and prevent urosepsis as well as assess levels of cognition, sensation in the distal lower extremities and gait function. Triheptanoin diet therapy is another possible treatment but, as of yet, the clinical benefits observed have been limited.
Prognosis
The prognosis is variable depending on the severity of the disease and the level of care given to patients. In most cases it does not decrease life-expectancy but quality of life is most definitely affected.

                            Last update: 
                            September 2012


                            - Expert reviewer(s): 
                            Pr Alexander LOSSOS