Pompe Disease
Pompe Disease
Pompe disease is a genetic condition. It happens when the body builds up too much of a sugar called glycogen in its cells. This buildup can affect certain organs and tissues, mainly muscles, making it hard for them to work normally. [1]
Symptoms
Symptoms of Pompe disease can be very different for different people, influenced by things like the person's age when the disease starts, the type of Pompe disease, and how quickly and severely the disease progresses. [2][3]
Some of the most common symptoms seen with Pompe disease include:
- Gradual decline in muscle strength
- Low muscle tone
- Breathing problems
- Respiratory infections
- Trouble eating
- Enlargement of the tongue, liver, and/or heart
- Difficulty hearing
There are three types of Pompe disease:
- Classic infantile-onset
- Non-classic infantile-onset
- Late-onset
Classic infantile-onset
Babies with classic infantile-onset Pompe disease start to show symptoms in the first few months after birth.They commonly face issues such as muscle weakness, low muscle tone, a larger liver, and heart issues. These babies may also struggle to gain weight and grow at the usual rate and have breathing problems. Without treatment, this form of Pompe disease leads to death from heart failure in the first year of life. [1][4]
Non-classic infantile-onset
In this form of Pompe disease, symptoms usually appear by age 1. It is described by delayed motor skills, such as rolling over and sitting, and a gradual decline in muscle strength. The heart may be larger than usual, but affected individuals usually do not experience heart failure. The muscle weakness in this disorder leads to significant breathing issues, and most children with non-classic infantile-onset Pompe disease live only into early childhood. [1][4]
Late-onset
Late-onset Pompe disease may not become clear until later in life, ranging from childhood to adulthood. This type of Pompe disease is generally less serious than the infantile-onset forms of this disorder and is less likely to involve the heart. Most individuals with late-onset Pompe disease experience a gradual decline in muscle strength, especially in the legs and the trunk, including the muscles that control breathing. As the disorder moves forward, breathing problems can lead to respiratory failure. [1][4]
Prevalence
Pompe disease occurs in different populations and ethnic groups, affecting about 1/40,000 people.[5] The populations that seem to be at higher risk include people of African American, Taiwanese, Dutch, and Israeli background.
Genetics
Mutations, or changes, in the GAA gene cause Pompe disease. The GAA gene provides instructions for making an enzyme called acid alpha-glucosidase (GAA). This enzyme works in lysosomes, which are like recycling centres within the cells of our body. The enzyme normally breaks down glycogen into a simpler sugar called glucose, which is the main energy source for most cells. [1][6]
A mutation in the GAA gene can either lead to the making of a GAA enzyme that doesn’t work correctly, or stop the enzyme from being made completely. This blocks acid alpha-glucosidase from breaking down glycogen well, which allows this sugar to build up to harmful levels in lysosomes. This buildup causes damage throughout the body, leading to the progressive signs and symptoms of Pompe disease. [1][6]
Close to 600 different GAA gene changes have been found in families with this disorder. You can find all the different types of the GAA gene in the Pompe variant database at: https://www.pompevariantdatabase.nl/ along with a description of how harmful they are and which forms of Pompe disease they are linked to.
Inheritance
Pompe disease is inherited in an autosomal recessive pattern.
Recessive genetic disorders happen when an individual inherits a gene that does not work from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease. Pompe disease carriers will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females. [7][8]
Diagnosis
Doctors might think someone has Pompe disease based on what they observe during a clinical examination, particularly findings related to breathing problems and signs of muscular weakness.
Confirming a diagnosis of Pompe disease usually involves enzymatic tests to measure the activity of the GAA enzyme. In children with infantile-onset Pompe disease, the activity of the GAA enzyme is generally less than 1% of normal. In individuals with the late-onset form of this disease, GAA activity is typically lower than 30% of normal. [4]
Genetic testing to look for mutations in the GAA gene that cause disease can help confirm the diagnosis, and is helpful in finding carriers. For people who are known carriers of the disease, genetic testing before the baby is born (prenatal testing) may be available and help ensure an early diagnosis. [2]
Management and Treatment
Pompe disease patients are usually cared for by a team of different specialists to make sure all parts of the disorder are treated. This team typically includes cardiologists, neurologists, pulmonologists, respiratory therapists, dieticians, orthopedists, occupational/speech therapists, geneticists, and genetic counsellors. [2]
Pompe disease treatment is based on:
- Disease-specific treatments, including enzyme replacement therapy
- Supportive therapies
Enzyme replacement therapy involves giving Pompe patients an engineered version of the GAA enzyme to replace the missing or nonworking enzyme. The treatment is designed to help lower the harmful buildup of glycogen inside cells, and slow the progression of the disease.
In addition to the disease-specific treatments, taking care of this condition involves treating symptoms and screening for complications. Non-drug treatments, such as physical therapy, occupational therapy, and speech therapy, may be of benefit for some people with Pompe disease. [5][4]
Genetic Counselling
An important part of the care by health care teams for patients with Pompe disease is genetic counselling. Genetic counselling helps people better understand medical recommendations and options available so they can make informed decisions. In addition to providing important information about the inheritance and genetic risks, genetic counselling also provides information about Pompe disease and available treatments and resources. If the GAA changes in an affected family member are known, carrier testing for at-risk family members, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible, and may be discussed with a genetic counsellor. [8][9][10]
Psychosocial Considerations
A diagnosis with Pompe disease can bring about emotional and social implications for individuals and their families. Managing Pompe disease often involves navigating through various challenges, and can evoke a range of emotions, including sadness, stress, and guilt. It is important to note that every individual and family will live with and cope with Pompe disease differently. Seeking the support of a genetic counsellor can provide valuable assistance in addressing the psychosocial aspects stemming from the experience with Pompe disease, providing a safe space for individuals and families to express their feelings, navigate decisional conflicts, and access appropriate resources for ongoing support.
Patient Resources
Canadian Association of Pompe
International Pompe Association
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 National Library of Medicine. (2016). Pompe Disease. Retrieved from https://medlineplus.gov/genetics/condition/pompe-disease/#inheritance
- ↑ 2.0 2.1 2.2 Wexler, M. (2023). Pompe Disease Overview. Pompe Disease News. https://pompediseasenews.com/what-is-pompe-disease/
- ↑ Güngör, D., & Reuser, A. J. J. (2013). How to describe the clinical spectrum in pompe disease? American Journal of Medical Genetics. Part A, 161A(2), 399-400. https://doi.org/10.1002/ajmg.a.35662
- ↑ 4.0 4.1 4.2 4.3 4.4 Van der Ploeg, Ans T, Dr, & Reuser, A. J., PhD. (2008). Pompe's disease. The Lancet (British Edition), 372(9646), 1342-1353. https://doi.org/10.1016/S0140-6736(08)61555-X
- ↑ 5.0 5.1 Stevens, D., Milani-Nejad, S., & Mozaffar, T. (2022). Pompe disease: A clinical, diagnostic, and therapeutic overview. Current Treatment Options in Neurology, 24(11), 573-588. https://doi.org/10.1007/s11940-022-00736-1
- ↑ 6.0 6.1 Peruzzo, P., Pavan, E., & Dardis, A. (2019). Molecular genetics of pompe disease: A comprehensive overview. Annals of Translational Medicine, 7(13), 278-278. https://doi.org/10.21037/atm.2019.04.13
- ↑ National Organization for Rare Disorders. (2021). Pompe Disease. Retrieved from https://rarediseases.org/rare-diseases/pompe-disease/#disease-overview-main
- ↑ 8.0 8.1 Leslie N, Bailey L. Pompe Disease. 2007 Aug 31 [Updated 2023 Nov 2]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews®. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1261/
- ↑ Atherton, A. M., Day-Salvatore, D., Pompe Disease Newborn Screening Working Group, & on behalf of the Pompe Disease Newborn Screening Working Group. (2017). The role of genetic counseling in pompe disease after patients are identified through newborn screening. Pediatrics (Evanston), 140(Suppl 1), S46-S50. https://doi.org/10.1542/peds.2016-0280F
- ↑ Taglia, A., Picillo, E., D'Ambrosio, P., Cecio, M. R., Viggiano, E., & Politano, L. (2011). Genetic counseling in pompe disease. Acta Myologica, 30(3), 179-181.