What Is Pompe Disease?

Pompe disease is a rare genetic disorder that’s caused by an inability to break down glycogen, a form of sugar that the body stores in the muscles for energy. As glycogen accumulates in toxic concentrations, it causes severe muscle weakness and tissue damage, impacting mobility, respiratory fitness, and heart health.

Pompe disease can be diagnosed at any age. The most severe form is diagnosed in infants, often soon after birth, during the routine newborn screening that occurs in most hospitals in the United States. The disease develops more slowly in older children and adults, though it can cause permanent muscle and tissue damage before it is diagnosed.

Types of Pompe Disease

• Infantile-onset (IOPD), which appears within the first year of life
• Late-onset (LOPD), which can be diagnosed at any other age, from early childhood to late adulthood

Both forms of the disease are characterized by a genetic deficiency of an enzyme called acid alpha-glucosidase (GAA). GAA is necessary to help break down glycogen, a complex sugar molecule stored in the muscle and organs, into simple glucose.

Infantile-Onset Pompe Disease

IOPD is the most severe and rapidly progressing form of the disorder. IOPD usually involves a near-total deficiency of the GAA enzyme, and its effects show up within the first days, weeks, or months of life.

• CRIM-positive infants should benefit from enzyme replacement therapy without complications.
• CRIM-negative infants lack any GAA at all, and their immune systems attack enzyme replacement medications as foreign substances. These children will need additional immune modulation medication to allow enzyme replacement therapy to work, and they may experience more significant developmental difficulties.

Late-Onset Pompe Disease

LOPD is a slower-moving form of Pompe disease that may be diagnosed at any age after the first year of life. In LOPD, a partial absence of GAA causes a slow accumulation of glycogen that primarily weakens the skeletal muscles, but usually does not lead to an enlarged heart. In younger children, LOPD may first manifest as clumsiness or lack of athleticism. In adults, it is best understood as a progressive muscle-wasting disorder.

Signs and Symptoms of Pompe Disease

At any age, Pompe disease leads to muscle weakness and breathing difficulties, though the exact nature of these symptoms will vary based on the age of the person with the condition.

Infancy

Among untreated infants, Pompe disease leads to physical weakness and failure to thrive, including:

• Muscle weakness or “floppiness”
• Slow growth or inability to gain weight
• Diminished reflexes
• Difficulty breathing or swallowing
• Enlarged tongue

Childhood

• Exercise intolerance
• Affected gait or posture, sometimes scoliosis
• Frequent respiratory infections
• Nasal voice
• Difficulty whistling or blowing
• Open-mouthed facial expression

The heart is usually unaffected in LOPD, even among younger children. And because the condition develops much less rapidly after the first year of life, it may take some time to recognize that the symptoms require medical treatment.

Adulthood

• Progressive weakness in the legs and trunk
• Difficulty breathing
• Difficulty exercising, walking, or climbing stairs
• Scoliosis
• Loss of balance
• Frequent lung infections
• Difficulty chewing or swallowing
• Gastrointestinal distress, including irritable bowel-like symptoms
• Diminished reflexes
• Chronic pain

Though treatment can significantly slow the development of these symptoms, the damage caused by untreated Pompe disease is mostly irreversible. Due to the combination of these symptoms, an individual with late-onset Pompe disease may become dependent on a wheelchair for mobility and require a breathing device, especially during sleep.

Causes and Risk Factors of Pompe Disease

Pompe disease is an inherited genetic disorder, meaning children inherit the genetic variants that cause it from their parents.

These variants are passed from generation to generation, although you don’t need to have Pompe disease to carry the mutation or pass it on to your children. Pompe disease is a recessive genetic disorder, which only occurs when you inherit a disease-causing variant from each parent. If both parents are carriers, each child has about a 25 percent change of developing the condition.

How Is Pompe Disease Diagnosed?

The diagnosis of Pompe disease usually begins with a test of GAA enzyme levels, which can be done with a simple blood sample. If the blood test shows an abnormally low concentration of GAA, your doctor may request a follow-up, such as a DNA test or muscle biopsy, to confirm a diagnosis of Pompe disease.

Treatment and Medication Options for Pompe Disease

The modern treatment of Pompe disease relies utterly on enzyme replacement therapy, though people with the condition may also require or benefit from a wide variety of supportive care measures to help with disease symptoms and complications such as mobility and breathing issues.

Enzyme Replacement Therapy

The one essential treatment for every form of Pompe disease is enzyme replacement therapy. This medication uses synthetic enzymes that have been designed to do the job of your missing or deficient GAA enzymes, helping your body to process glycogen.

Enzyme replacement can slam the brakes on physical decline, slowing, halting, or even slightly reversing the development of breathing problems and mobility challenges. In infants, enzyme replacement therapy can also rapidly reverse a life-threatening thickened heart.

• Alglucosidase Alfa (Myozyme/Lumizyme) This is the original enzyme replacement therapy for Pompe disease and remains the first-line therapy for most people with the condition; it is still the only treatment approved for infants with Pompe disease.
• Avalglucosidase Alfa (Nexviazyme) This is a newer enzyme replacement that targets the muscles more effectively and may deliver superior breathing and mobility improvements to people with LOPD.
• Cipaglucosidase Alfa + Miglustat (Pombiliti + Opfolda) This is the newest treatment for LOPD, which combines an enzyme with a stabilizer, and it is approved for adults who are not improving on a different form of enzyme replacement therapy.

These drugs require a lifelong commitment to regular lengthy infusion sessions. The medications are delivered through a slow intravenous drip, which requires sitting still for a period of up to seven hours, whether at home, in a hospital, or in a specialized infusion center, generally once every two weeks.

Enzyme replacement therapy is not a cure-all for Pompe disease. Some people who respond well to the treatment will still experience health declines over the years. These medications are too new to know what their overall effect on life expectancy is.

Immune Tolerance Induction for CRIM-Negative IOPD

Infants who are CRIM-negative lack any GAA at all, and their immune systems will identify enzyme replacements as invaders to be attacked. These children require a protocol named immune tolerance induction to retrain their bodies to accept life-saving enzyme replacement therapy. While beginning enzyme replacement therapy, CRIM-negative infants will also need a number of additional medications to target different parts of the immune system.

Supportive Care

In addition to ERT, your care team — including cardiologists, respiratory therapists, and neurologists, among others — can help you come up with a treatment plan that manages your symptoms and provides any supportive care you may need, such as assistance with mobility and maintaining healthy breathing.

• Breathing support, including supplemental oxygen or breathing devices such as the use of a BiPAP machine overnight
• Physiotherapy to improve muscle strength and function
• Occupational therapy to maintain independence in daily activities such as dressing and eating
• Speech therapy to make speaking and swallowing easier
• Adaptive mobility devices such as walkers, canes, or wheelchairs

Lifestyle Changes for Pompe Disease

In addition to specialized medical care and support, people with Pompe disease may be advised to follow specific diet and exercise regimens.

Diet

Nutritional management in Pompe disease is a balancing act of maintaining lean muscle mass and preventing malnutrition while also preventing obesity, which may be more common, due to reduced physical activity.

Some people with Pompe disease may not have the muscle strength to chew or swallow easily, and may require finely chopped foods, a liquid diet, or a feeding tube.

Exercise

While historically Pompe disease patients were cautioned against overexertion to avoid muscle damage, experts now see exercise as an important addition to medical therapy:

• Resistance training can help combat progressive muscle weakness, improving strength and function, such as walking capacity.

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• Low-impact aerobic exercise can help support both cardiovascular health and respiratory function.

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Every individual with Pompe disease will have unique physical abilities and challenges, and the choice of any exercise regimen should be made in collaboration with a care team.

Pompe Disease Prognosis

Pompe disease is a lifelong condition, and symptoms may worsen over time, even with enzyme replacement therapy. These declines generally lead to worsening quality of life, and if heart or lung function declines, may lead to early death.

IOPD Prognosis

LOPD Prognosis

The advent of enzyme replacement therapy has undoubtedly improved the life expectancy of everyone with LOPD, but it may still be years before we can reliably estimate its ultimate effect on those who receive treatment.

Complications of Pompe Disease

• Mobility loss
• Breathing difficulties
• Skeletal deformities, including scoliosis
• Swallowing difficulties
• Speech difficulties
• Enlarged tongue
• Enlarged liver
• Hearing loss
• Droopy eyelids

In adults who have developed LOPD, these complications generally take the form of a slow decline. But in younger children with either IOPD or LOPD, they could mean a failure to ever hit age-appropriate benchmarks, such as stunted growth and the inability to walk independently.

Support for Pompe Disease

A diagnosis of Pompe disease can be overwhelming for both patients and their caregivers. Support groups and advocacy networks can help you difficult navigate the challenges to come:

United Pompe Foundation

This organization was formed to assist patients and their families with Pompe disease–related medical costs and other expenses that may not be covered by insurance.

Pompe Alliance

This organization provides supportive services, education, and information to patients and caregivers, organizes advocacy events, and connects users with providers with experience treating Pompe disease.

Acid Maltase Deficiency Association

This advocacy group, which was founded by a family affected by Pompe disease, tries to advance research and improve care for people with the condition.

International Pompe Association

A global federation of patient groups, this organization encourages families to communicate with each other to improve the quality of life of people with Pompe disease.