Why is APBD Misdiagnosed as MS or ALS? Key Differences

Adult Polyglucosan Body Disease (APBD) is frequently mistaken for Multiple Sclerosis (MS) or Amyotrophic Lateral Sclerosis (ALS) because it shares the same core symptoms—such as leg stiffness and bladder issues—and similar abnormalities on brain imaging ^[1]. Because APBD is a rare genetic disorder, neurologists naturally suspect common diseases like MS or ALS first. It often takes years of ruling out these conditions and dealing with incorrect treatments before specialized testing correctly identifies APBD ^[1].

Symptom Overlap: The Clinical Mimic

APBD typically begins in adulthood with a specific trio of symptoms: progressive spastic paraparesis (increasing leg stiffness and weakness), neurogenic bladder (loss of bladder control causing urinary urgency or incontinence), and peripheral neuropathy (nerve damage in the lower legs causing numbness or tingling) ^[2][3].

• Why it looks like MS: Primary Progressive MS commonly causes the exact same combination of progressive leg stiffness and bladder dysfunction as its first symptoms ^[1].
• Why it looks like ALS: ALS involves the degeneration of upper motor neurons (causing spasticity and brisk reflexes) and lower motor neurons (causing muscle weakness and wasting). The combination of APBD’s upper motor neuron signs (stiff legs) and peripheral nerve damage closely mimics the progressive motor decline seen in ALS or Primary Lateral Sclerosis (PLS) ^[4]. However, ALS typically does not cause sensory numbness or bladder issues. In APBD, severe motor weakness often drives the initial suspicion of ALS, but the presence of sensory and bladder symptoms eventually prompts doctors to reconsider their diagnosis and look further.

MRI Overlap: White Matter Changes

Brain scans are usually what lead a neurologist toward a misdiagnosis of MS. An MRI of a patient with APBD typically shows leukoencephalopathy—abnormal changes or damage in the brain’s white matter ^[1][5].

In APBD, abnormal glycogen (polyglucosan bodies) accumulates in the brain’s support cells (astrocytes) and neurons ^[6][7]. On an MRI, this damage appears as bright spots (hyperintensities) in the periventricular regions (areas around the brain’s fluid-filled spaces) and the brainstem ^[3][1]. Because MS also causes bright spots in these exact same regions due to demyelination (loss of the protective coating on nerves), radiologists frequently interpret the APBD scan as MS ^[1][6].

Another overlapping MRI finding is spinal cord atrophy (shrinking of the spinal cord), which is seen in both MS and APBD ^[1]. However, shrinking of the upper spinal cord (cervical spine) and the lower brainstem (medulla) is a nearly universal feature in APBD ^[3]. This consistent shrinking can be a key clue for an expert radiologist differentiating between the diseases.

Reaching the Right Diagnosis

This clinical and imaging overlap is why the APBD diagnostic journey is often long and deeply frustrating ^[8][1]. It validates why so many patients spend years with an MS or ALS label before finding the truth.

The key to finally distinguishing APBD from MS or ALS is specialized testing. While a lumbar puncture (spinal tap) in MS often shows specific inflammatory markers called oligoclonal bands, these are absent in APBD. Instead of relying only on symptoms and imaging, a definitive diagnosis requires genetic testing to look for mutations in the GBE1 gene ^[3]. If genetic testing is inconclusive, doctors can also measure the activity of the glycogen branching enzyme in a blood sample, or perform a skin or nerve biopsy to physically look for the abnormal polyglucosan bodies under a microscope.

What Happens After an APBD Diagnosis?

After finally receiving an accurate diagnosis, you will need to transition your care. While you may continue seeing a general neurologist, it is highly recommended to involve specialists familiar with rare genetic or metabolic disorders (such as a neurogeneticist).

Because APBD is an inherited condition, genetic counseling is essential to help you understand what this diagnosis means for your siblings, children, and extended family members.

Although there is currently no cure for APBD, a multi-disciplinary care team can actively manage your symptoms. This team typically includes physical therapists to help with mobility and leg stiffness, and urologists to manage bladder function and preserve kidney health. Finding rare disease support groups or patient registries can also connect you with a community that understands this unique diagnostic journey.