Pompe Disease

Pompe Disease, also known as glycogen storage disease type II, is a rare genetic disorder that affects the muscles and their ability to function properly. It is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA), which is responsible for breaking down glycogen, a complex sugar molecule, into simpler forms that the body can use for energy. This deficiency leads to the accumulation of glycogen in various tissues, particularly in muscles, impairing their function.

Understanding this rare genetic disorder is crucial if you or your child are affected. Each case varies, but there are medical treatments available to manage symptoms effectively.

Pompe disease arises when the body is unable to produce a protein essential for breaking down glycogen, a complex sugar used for energy. The accumulation of excess sugar leads to muscle and organ damage.

Symptoms of this rare genetic disorder include muscle weakness and respiratory difficulties, primarily impacting the liver, heart, and muscles. While Pompe disease can affect anyone, it’s more prevalent among African-American individuals and certain Asian populations.

Causes

Pompe Disease is caused by mutations in the GAA gene, which is responsible for producing the acid alpha-glucosidase enzyme. These mutations can be inherited from one or both parents, or they can occur spontaneously. To develop the condition, one must inherit two defective genes, one from each parent. It’s possible to carry one flawed gene without experiencing symptoms of the disease.

Prevalence

Pompe Disease is considered a rare disorder, with an estimated incidence of about 1 in 40,000 births worldwide. However, the prevalence may vary among different populations and regions.

Symptoms of Pompe disease

The symptoms of this rare genetic disorder can vary greatly among individuals in terms of onset, severity, and impact.

Early-onset, or infantile, Pompe disease typically manifests in babies between a few months old and up to age 1. Signs may include:

• Difficulty feeding and inadequate weight gain
• Poor control of the head and neck
• Delayed achievement of developmental milestones like rolling over and sitting up
• Respiratory issues and frequent lung infections
• Enlargement and thickening of the heart or congenital heart defects
• Enlarged liver
• Enlarged tongue

Late-onset of this rare genetic disorder can begin as late as in one’s 60s, progresses slowly, and often does not involve heart complications. Common symptoms may include:

• Weakness in the legs, trunk, and arms
• Shortness of breath, particularly during exertion, and susceptibility to lung infections
• Breathing difficulties during sleep
• Development of a noticeable spinal curvature
• Enlarged liver
• Enlarged tongue, leading to difficulties with chewing and swallowing
• Stiff joints

Risk Factors

The primary risk factor for Pompe Disease is having a family history of the condition, as it is an inherited disorder. However, spontaneous mutations can also occur in individuals with no family history of the disease.

Diagnosing Pompe disease

Diagnosing this rare genetic disorder can be challenging due to overlapping symptoms with other conditions. Your doctor may inquire about:

• Weakness, falls, or difficulties with mobility
• Breathing issues, especially nocturnal or when lying down
• Morning headaches
• Daytime fatigue
• Childhood health history
• Family history of similar health problems

Tests may be necessary to rule out other conditions, and if Pompe disease is suspected, confirmation typically involves:

• Muscle biopsy to assess glycogen levels
• Blood sample analysis to evaluate the function of the defective protein(GAA)
• Genetic testing to identify the specific genetic mutation associated with this rare genetic disorder.

Diagnosis can take several months for infants and several years for children and adults. Following confirmation, it’s advisable to screen family members for the genetic mutation.

Questions for Your Doctor:

• What can I anticipate in the future regarding my condition?
• What are the most suitable treatment options for me presently? Are there any clinical trials available that I should consider?
• Do the recommended treatments have any potential side effects, and how can they be managed?
• How will my progress be monitored, and are there any new symptoms I should be vigilant about?
• How frequently should I schedule follow-up appointments with you?

Treatments for Pompe disease

Early intervention, particularly for infants, plays a crucial role in mitigating the progression of damage within the body. Enzyme replacement therapy (ERT) is instrumental in enhancing survival rates and improving cardiac and motor functions.

Three medications are utilized to supplement the deficient protein and aid in the proper processing of sugar, administered via injection:

• Lumizyme
• Myozyme, designed for infants and children
• Nexviazyme is intended for individuals aged 1 year and older with late-onset of this rare genetic disorder.

For adults experiencing late-onset Pompe disease unresponsive to enzyme replacement therapy (ERT), the FDA has approved a novel treatment combining two medications. This treatment involves the administration of injectable ERT cipaglucosidase alfa-atga (Pombiliti) alongside miglustat (Opfolda), an enzyme stabilizer available in capsule form. Pombiliti + Opfolda is indicated for individuals weighing at least 88 pounds. However, the safety and efficacy of this combination treatment for children remain uncertain.

Home Care Tips

In addition to medical treatment, individuals with this rare genetic disorder can benefit from various home care strategies to manage their symptoms and improve daily functioning. These may include:

• Following a healthy diet to maintain energy levels and muscle strength
• Engaging in regular physical activity within the limits of one’s abilities
• Using assistive devices, such as braces or mobility aids, to aid in mobility
• Practicing respiratory exercises to improve lung function and prevent respiratory infections

Prevention of Pompe disease

Since Pompe Disease is a genetic disorder, it cannot be prevented. However, genetic counseling may be recommended for individuals with a family history of the condition to assess the risk of passing it on to future generations.

Expectations

Given the multisystemic impact of this rare genetic disorder, comprehensive care by a team of specialists well-versed in the condition is paramount. This may include:

• Cardiologist
• Neurologist
• Respiratory Therapist
• Nutritionist

Generally, the onset of Pompe disease later in life corresponds to a slower disease progression. While infants can undergo treatment, their symptoms are typically more severe and progress rapidly, resulting in a lifespan of less than a year. Late-onset Pompe disease manifests with progressive muscle weakness over time, eventually leading to significant respiratory complications, often occurring many years later.

Although Pompe disease lacks a cure, symptom management through treatment modalities can extend lifespan and improve quality of life.

When to See a Doctor

If you or your child are experiencing symptoms suggestive of Pompe Disease, such as muscle weakness, respiratory problems, or cardiomegaly, it is important to see a doctor for further evaluation and diagnosis. Early detection and treatment can help improve outcomes and quality of life for individuals with Pompe Disease.

Outlook/Prognosis

The prognosis for individuals with Pompe Disease varies depending on the age of onset, the severity of symptoms, and the response to treatment. With early diagnosis and appropriate management, many people with Pompe Disease can lead fulfilling lives and maintain a good quality of life.

Sources

1. National Institute of Neurological Disorders and Stroke. (2022). Glycogen Storage Disease Type II (Pompe Disease).
2. AGSDUS. Glycogen and Glycogen Storage Diseases and Type II Glycogen Storage Disease.
3. Duke Children’s Hospital & Health Center. Pompe Disease Clinical and Research Program.
4. NIH. Pompe disease.
5. Emory University. Pompe Disease.
6. Kishnani, P. American Journal of Medical Genetics Part C (Seminars in Medical Genetics), 2012.
7. Genetics Home Reference. (2022). Pompe Disease.