Clinical Guidance

No clear correlation of clinical severity and GBE1 pathogenic variants is known.

Source: GeneReviews — "GBE1 Adult Polyglucosan Body Disease"

Diagnostic Criteria

Suggestive Findings

GBE1 adult polyglucosan body disease (GBE1-APBD) should be considered in individuals with the following clinical findings, neuroimaging findings, family history, and ethnicity.

Clinical findings

• Onset age ≥40 years

• Progressive neurogenic bladder

• Gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement

• Sensory loss predominantly in the distal lower extremities

• Mild difficulties in cognition (often executive dysfunction)

• A history of infantile liver disease

Brain and spinal cord MRI

Source: GeneReviews — "GBE1 Adult Polyglucosan Body Disease"

Differential Diagnosis

Delay in diagnosis of GBE1 adult polyglucosan body disease (GBE1-APBD) is common because multiple sclerosis and primary urologic dysfunction are most commonly considered first. Other disorders that may present similarly to GBE1-APBD include amyotrophic lateral sclerosis, cerebral small vessel disease (e.g., CADASIL, HTRA1 disorder, and COL4A1 and COL4A2-related small vessel disease), and peripheral neuropathies (e.g., Charcot-Marie-Tooth hereditary neuropathy) . These disorders can be excluded based on clinical findings because none exhibits the combination of pyramidal spastic paraparesis and peripheral neuropathy seen in nearly all individuals with GBE1-APBD. Polyglucosan bodies. In adult polyglucosan body disease (GBE1-APBD), the polyglucosan bodies consist of periodic acid-Schiff (PAS)-positive material with diastase-resistant glucose polymers and are seen in the central and peripheral nervous system. In early infantile-onset glycogen storage disease type IV , polyglucosan bodies most commonly accumulate in the liver, heart, muscle, brain, spinal cord, peripheral nerve, and skin. Other genes associated with polyglucosans are summarized in . Table 3. Other Genes Associated with Accumulation of Polyglucosan Bodies

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with GBE1 adult polyglucosan body disease (GBE1-APBD), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Recommended Evaluations Following Initial Diagnosis in Individuals with GBE1 Adult Polyglucosan Body Disease

System/Concern | Evaluation | Comment

Neurologic

| Complete neurologic exam | • Obtain history for stroke-like episodes.

• Assess for UMN (spasticity) LMN involvement (weakness sensory loss).

• Brain spine MRI (if not obtained at time of diagnosis) to exclude other causes of gait spasticity neurogenic bladder

Musculoskeletal

| Orthopedics / physical medicine rehab / PT eval | To incl assessment of:

• Muscle tone; joint range of motion; posture; mobility; strength, coordination endurance; pain; bedsores

• Need for adaptive devices

• Footwear needs

• PT needs

OT eval | To assess:

• Small motor function (hands, feet, face, fingers, toes)

• ADL

Bladder function

| History of spastic bladder symptoms: urgency, frequency, difficulty voiding | • Referral to urologist

• Consider urodynamic eval imaging of urinary tract kidneys.

Orthostatic

hypotension | History of postural dizziness syncope | Test blood pressure for postural changes.

Constipation

| History of constipation | Gastroenterology eval

Cognitive

Source: GeneReviews — "GBE1 Adult Polyglucosan Body Disease"

Therapies Under Investigation

Clinical trials involve use of guaiacol and triacyglycerol mimetic 5 (TGM5) . Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "GBE1 Adult Polyglucosan Body Disease"

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with GBE1 Adult Polyglucosan Body Disease

Source: GeneReviews — "GBE1 Adult Polyglucosan Body Disease"