Adult polyglucosan body disease

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Adult polyglucosan body disease (APBD) is a condition that affects the nervous system. People with APBD typically first experience signs and symptoms related to the condition between ages 35 and 60. Initial symptoms of the disorder include numbness and tingling in the legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). As a result, affected individuals can have an unsteady gait, poor balance, and an increased risk of falling.

Damage to the nerves that control bladder function, a condition called neurogenic bladder, is another feature that often occurs early in the course of APBD. Affected individuals have increasing difficulty starting or stopping the flow of urine.

Eventually, most people with APBD lose the ability to control their bladder and bowel functions and their limbs. Damage to the autonomic nervous system, which controls body functions that are mostly involuntary, leads to problems with blood pressure, heart rate, breathing rate, digestion, temperature regulation, and sexual response, and results in daily bouts of exhaustion. About half of people with APBD experience a decline in intellectual function (dementia).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the GBE1 gene cause APBD. The GBE1 gene provides instructions for making the glycogen branching enzyme. This enzyme is involved in the production of a complex sugar called glycogen, which is a major source of stored energy in the body. Most GBE1 gene mutations that cause APBD result in a shortage (deficiency) of the glycogen branching enzyme, which leads to the production of abnormal glycogen molecules. These abnormal glycogen molecules, called polyglucosan bodies, accumulate within cells and cause damage. Nerve cells (neurons) appear to be particularly vulnerable to the accumulation of polyglucosan bodies in people with this disorder, leading to impaired neuronal function.

Some mutations in the GBE1 gene that cause APBD do not result in a shortage of glycogen branching enzyme. In people with these mutations, the activity of this enzyme is normal. How mutations cause the disease in these individuals is unclear. Other people with APBD do not have identified mutations in the GBE1 gene. In these individuals, the cause of the disease is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

APBD is a rare condition, although its exact prevalence is unknown. Approximately 200 affected individuals have been diagnosed worldwide. Recently these have included younger individuals who have not yet experienced signs or symptoms but who are diagnosed in the course of genetic screening when considering parenthood. Researchers suspect that the disorder may be underdiagnosed.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal pyramidal sign · Very frequent (99-80%)

Functional neurological abnormalities related to dysfunction of the pyramidal tract.

Gait disturbance · Very frequent (99-80%)

The term gait disturbance can refer to any disruption of the ability to walk.

Hemiparesis · Very frequent (99-80%)

Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength.

Intellectual disability · Very frequent (99-80%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Muscle weakness · Very frequent (99-80%)

Reduced strength of muscles.

Neurogenic bladder · Very frequent (99-80%)

A type of bladder dysfunction caused by neurologic damage. Neurogenic bladder can be flaccid or spastic. Common manifestatios of neurogenic bladder are overflow incontinence, frequency, urgency, urge incontinence, and retention.

Peripheral neuropathy · Very frequent (99-80%)

Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.

Spasticity · Very frequent (99-80%)

A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.

Urinary bladder sphincter dysfunction · Very frequent (99-80%)

Abnormal function of a sphincter of the urinary bladder.

Urinary incontinence · Very frequent (99-80%)

Loss of the ability to control the urinary bladder leading to involuntary urination.

Atypical behavior · Frequent (79-30%)

Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.

Distal sensory impairment · Frequent (79-30%)

An abnormal reduction in sensation in the distal portions of the extremities.

Skin ulcer · Frequent (79-30%)

A discontinuity of the skin exhibiting complete loss of the epidermis and often portions of the dermis and even subcutaneous fat.

Abnormality of extrapyramidal motor function · Occasional (29-5%)

A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).

Other findings in the same source

From: Orphanet

Additional reported features include Ataxia (Occasional (29-5%)); Dementia (Occasional (29-5%)); EMG abnormality (Occasional (29-5%)); Limitation of joint mobility (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Adult polyglucosan body disease is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Adult polyglucosan body disease. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.