Overview 

Pompe disease is a genetic disorder that is characterised by the gradual loss of muscular strength, with the skeletal and cardiac muscles being the most at risk of weakness. Pompe disease has a destructive nature that creates many challenges for both the individuals with the disease and their families. Alongside muscle weakness, research suggests that hearing impairments are associated with the childhood form of Pompe disease.¹ This article aims to highlight the key causes and symptoms of Pompe disease and how hearing can be affected. 

Pompe disease

Causes 

Pompe disease is caused by mutations to the gene that makes an enzyme called acid alpha-glucosidase (GAA).² Enzymes are tiny machine-like structures that can have a range of functions, such as breaking big molecules into smaller pieces, building new proteins and speeding up chemical reactions in the body.³

In healthy individuals, GAA is a digestive enzyme that breaks down a molecule called glycogen. We do not always need the sugar we eat in our diet immediately, therefore it is stored in chains of glycogen that acts as an energy reserve. 

Mutations in GAA mean that the enzyme is unable to perform its function of breaking down glycogen into sugar.⁴ Therefore, individuals with Pompe disease have a buildup of glycogen in lysosomes, which are compartments within cells. This buildup can happen across all cells of the body, but skeletal muscles are particularly affected.² 

Types and symptoms

Infantile-onset Pompe disease

There are two main types of Pompe disease, with infantile-onset Pompe disease (IOPD) being the most serious form of the genetic disorder. This affects children under the age of 12 months and is caused by complete dysfunction of GAA.⁵ Worldwide, approximately 1 in every 40,000 newborns are affected by IOPD.⁶ If left untreated, IOPD can be fatal in the first year of life.⁷

The symptoms of IOPD include:²

• Muscle weakness, causing individuals difficulties with supporting their head and body 
• Feeding problems, resulting in minimal weight gain 
• Heart problems, causing heart enlargement
• Breathing difficulties 
• Enlarged tongue
• Hearing problems 
• Delayed motor skill development 

Late-onset Pompe disease

Whilst the name suggests onset in adulthood, late-onset Pompe disease (LOPD) can occur from the age of 1 year old, as well as extending into adulthood. This form of Pompe disease is less destructive, as the GAA enzyme is only partially dysfunctional.⁵ As there is some degree of glycogen breakdown, the symptoms tend to be less severe and progress much slower when compared to IOPD. 

Aside from the age of onset, another key difference between IOPD and LOPD is the associated heart problems. Whilst muscle weakness is still a large factor in LOPD, the heart is usually unaffected.⁵ The symptoms of LOPD include:²

• Gradual loss of muscle strength
• Falling over frequently 
• Shortness of breath
• Unintended weight loss 
• Hearing problems

The auditory system

The auditory system is made up of external and internal structures that work together to allow us to hear and understand the sounds of our surroundings. The ear is made up of 3 main parts: the outer, middle and inner ear.⁸

• The outer ear is the visible part of the ear, responsible for collecting sound and ushering it into the ear canal where the sound is amplified. The end of the ear canal is called the eardrum, which begins to vibrate when the amplified sound waves reach it
• The middle ear is made up of 3 bones (called the ossicles), which are the smallest bones in the human body. These move in response to the vibrations from the eardrum
• The inner ear consists of the cochlea, semi-circular canals and the vestibule. The cochlea is a snail-shaped organ that is filled with fluid which ripples in response to vibrations. Hair cells in the cochlea move up and down in response to these vibrations. Depending on their location within the cochlea, the hair cells can detect different pitches
• The smaller projections on top of each hair cell bend side to side. The bending of these small projections causes the release of chemical signals. The cochlear nerve carries this sensory information from the cochlea to the brain for processing, allowing us to hear and understand sound⁹

Types of hearing loss in Pompe disease

There are two types of hearing loss associated with the onset of Pompe disease. These are:¹⁰

• Conductive
• Sensorineural

Conductive hearing loss occurs when there is a problem delivering sound waves to the cochlea. This could be through blockages of the ear canal, damage to the ossicle bones in the middle ear, or an issue with the eardrum.¹¹ The main role of the outer and middle ear is to amplify, or louden, sound waves.⁸ Problems with these sections of the ear reduce the volume of sound waves that reach the cochlea, resulting in hearing loss. 

Sensorineural hearing loss is characterised by problems related to the cochlea and the auditory nerve. Whilst this can happen for many reasons, it is believed that a buildup of glycogen in the cochlea is responsible for this type of hearing impairment in Pompe disease.¹¹ Like with damage to the skeletal and cardiac muscle cells, glycogen buildup can damage the tiny hair cells in the cochlea. This damage disrupts auditory information travelling from the cochlea to the brain, which causes hearing loss or impairments. 

Hearing loss and impairments have mainly been recorded in individuals with IOPD, with 91% of infants with the disease having sensorineural hearing deficits.¹¹ Spotting signs of hearing impairment early on in IOPD is vital to provide infants with the best chance of adapting to the use of hearing aids or cochlear implants.¹⁰ 

Whilst there are reports of hearing loss in LOPD, the prevalence is similar to that of the general population. This means that hearing deficits in adults with LOPD are not specifically related to the disease.¹

Treatments

Enzyme replacement therapy 

The main treatment that is currently used for Pompe disease is enzyme replacement therapy (ERT). ERT involves injecting the enzyme GAA directly into the bloodstream of the affected individual, to replenish its levels.⁶

As a result of this treatment, the body can break down glycogen stores to prevent the buildups that otherwise trigger the symptoms of Pompe disease. Whilst this treatment is effective in slowing down progression and helping to alleviate the associated symptoms, individuals will have to receive ERT for the rest of their lives.¹² Additionally, there is no evidence to suggest ERT helps to reduce hearing loss in those affected by Pompe disease.¹³

Hearing aids and cochlear implants

Whilst not specific to hearing loss in Pompe disease, hearing aids and cochlear implants are widely used to help those afflicted with hearing difficulties. The use of which aid depends on the type of hearing loss. 

Hearing aids are used for conductive hearing loss or impairments. They often sit behind the ear, attached to a moulded piece of plastic that fits inside the ear. The microphone on the hearing aid picks up sound and amplifies the sound waves for your cochlea, which then sends signals along the auditory nerve for processing in the brain.¹⁴

Cochlear implants are used when hearing loss is sensorineural, which tends to be severe, where regular hearing aids have not helped. As the name suggests, cochlear implants involve a device that is placed inside the skull. This magnetic implant can detect sound picked up from a microphone attached behind the ear. These sound waves are converted into electrical signals which are transported on wires to the cochlea to be processed in the brain.¹⁵

Summary

As a rare genetic disorder, Pompe disease can be a life-threatening condition – particularly for those in their first year of life, where the heart is more at risk of damage from the buildup of glycogen. Whilst not recognised as a specific feature of LOPD, there is an established risk of hearing loss in those with the infantile form of Pompe disease.

Although enzyme replacement therapy has been proven to reduce the symptoms and progression of disease, its effect on hearing requires much more research. Depending on the type of impairment, hearing aids and cochlear implants remain the most effective method of regaining hearing.