|Year : 2015 | Volume
| Issue : 2 | Page : 19-22
Pompe disease: A rare clinical entity
Associate Professor, Sri B.M. Patil Institute of Nursing Science, Bijapur
|Date of Web Publication||23-May-2020|
Source of Support: None, Conflict of Interest: None
Genes control many aspects of the body, including production of important enzymes. Every gene in the body comes as a pair. One copy is passed on by the father and one by the mother. Changes to a normal DNA makeup can result in a defect, also called a mutation in the gene, which can cause the gene to function improperly. In Pompe disease and other similar disorders, a gene mutation causes a deficiency or malfunction of a necessary enzyme. The combination of Glucosidase Acid Alpha (GAA) genes inherited from both parents determines whether a person will be affected by Pompe disease. Although Pompe disease is very rare, it can run in families because it is inherited, meaning that it gets passed on to people through their parents. If someone is diagnosed with the disease, there is a risk that relatives may also have the disease or be carriers. It is particularly important to test siblings of an affected child. Hence genetic counseling plays an important role in care of child and their family members. A brief account of its etiology, pathogenesis, clinical features, diagnosis, and management is provided in this article. The nursing management including role of a nurse as a care coordinator is also discussed using exemplars.
Keywords: gene, GAA enzyme, Pompe disease, mutation, inheritance, autosomal recessive disease
|How to cite this article:|
Kavitha K. Pompe disease: A rare clinical entity. Indian J Cont Nsg Edn 2015;16:19-22
| Introduction|| |
Pompe disease is a rare, progressive, and often fatal inherited disease with irreversible pathology caused by deficiency of lysosomal acid alpha-glucosidase which results in buildup of a complex sugar called glycogen in the muscles, certain organs and tissues, that impairs their ability to function normally. It is also referred to as glycogen storage disease type II (GSD-II), acid maltase deficiency (AMD), glycogenesis type II, alpha-1,4-glucosidase deficiency, and GAA deficiency disorder. The disease is named after Joannes Cassianus Pompe, who characterized it in 1932. The gene responsible for Pompe disease was identified in 1979 and named glucosidase acid alpha (GAA). Pompe described accumulation of glycogen in muscle tissue in some cases of a previously unknown disorder. This accumulation was difficult to explain as the enzymes involved in the usual metabolism of glucose and glycogen were all present and functioning. The abbreviation GAA is often used interchangeably to refer to both the gene and the enzyme involved in Pompe disease (Wikipedia, 2015).
| Etiology|| |
Pompe disease is inherited in an autosomal recessive manner. Thus, both parents of a child with the disease must be carriers of a mutant gene for GAA, and each child born to them has a 25% chance of having the disease, a 50% chance of being a carrier, and a 25% chance of neither having the disease nor being a carrier. The common mutants are Asp64Gkn (common among Taiwanise); ARg854X (African-Americans); del525T (Dutch); delexon 18 (Dutch); IVS 1-13t>gsplice (Caucasians). Pompe disease may be classified into classic infantile onset (1/1,38,000 live births), non-classic infantile onset, and late onset (1/51,000 live births). The Overall onset of Pompe disease is 1/40, 000 live births. But the incidence varies with ethnic groups, highest among Africans and lowest among Chinese (Genzyme, 2005).
| Pathogenesis|| |
GAA is essential for degradation of lysosomal glycogen. Deficiency of GAA causes accumulation of glycogen and distension in the muscles. Myofibrils are replaced by glycogen which eventually leads to tissue destruction. The most common organs involved in glycogen storage are: cardiac muscles, proximal skeletal muscles of trunk and lower leg, and respiratory muscles (Genzyme, 2005). The impaired lysosomal degradation is illustrated in [Figure 1].
|Figure 1: Impaired lysosomal degradation in Pompe disease (Source: Genzyme, 2005)|
Click here to view
| Clinical features|| |
The common clinical manifestations include delayed motor development, muscle weakness, and cardiomegaly. The variations in clinical features according to type of Pompe disease is described in [Table 1].The types are categorized into three namely classic infantile onset, Nonclassic infantile onset, and late onset Pompe disease. (National Institute of Neurological Disorders and Stroke, 2013).
| Diagnostic Measures|| |
A diagnosis of Pompe disease can be confirmed by screening for the common genetic mutations or measuring the level of GAA enzyme activity in a blood sample. Once Pompe disease is diagnosed, testing of all family members and consultation with a professional geneticist are recommended. Carriers are most reliably identified via genetic mutation analysis. Other diagnostic measures are echocardiography and electrocardiogram (Kleigman, Stanton, Geme, Schor, & Behrman, 2012).
| Treatment|| |
Individuals with Pompe disease are best treated by a team of specialists (such as cardiologist, neurologist and respiratory therapist) knowledgeable about the disease, who can offer supportive and symptomatic care. The discovery of the GAA gene has led to rapid progress in understanding the biological mechanisms and properties of the GAA enzyme. As a result, an enzyme replacement therapy has been developed that has shown, in clinical trials with infantileonset patients, to decrease heart size, maintain normal heart function, improve muscle function, tone and strength, and reduce glycogen accumulation. A drug called alglucosidase alfa (Myozyme), has received Food and Drug Administration approval in US for the treatment of infants and children with Pompe disease. Another alglucosidase alfa drug, Lumizyme, has been approved for late-onset (non-infantile) Pompe disease (Muscular Dystrophy Association, 2015).
| Prognosis|| |
Without enzyme replacement therapy,the hearts of babies with infantile onset Pompe disease progressively thicken and enlarge. These babies die before the age of one year from either cardiorespiratory failure or respiratory infection. For individuals with late onset Pompe disease, the prognosis is depending upon the age of onset. In general the later the age of onset, the slower the progression of disease. Ultimately, the prognosis depends upon the extent of respiratory muscle involvement (Wagner, 2007).The following case study reports are examples of the disease manifestations, progress, and outcomes.
| Exemplars|| |
Case 1: A 4 months old infant got admitted in a Medical College, Bijapur, with the chief complaints of failure to thrive, lack of muscle tone, breathing difficulty. On examination infant was found to be floppy with complete headlag. Radiological examination revealed cardiomyopathy and ECG changes (Decreased PR interval).The history revealed that the infant is the only child for his parents. He is from a nuclear family and the parents had a second degree consanguineous marriage. Father is a coolie and earns about ₹ 2000/- a month. The infant was diagnosed to have pompe disease. The parents were informed about the rare clinical entity and the treatment option myozyme. Due to the financial burden the child was not able to be on regular treatment. After 2 doses of Myozyme, the child missed the 3rd dose for nearly one month and eventually he developed respiratory failure and died at the age of 6 months.
Case 2: A 4 months, girl infant got admitted in a medical College, Bijapur, with chief complaints of failure to thrive, respiratory tract infection associated with breathing difficulty, lethargy, and muscle weakness. The family history revealed that the parents had a second degree consanguineous marriage. She is the second child of her parents. She has an elder brother who is healthy with normal developmental milestones. Regarding socioeconomic status her father ,a business man earns around ₹ 15,000/- a month. After clinical examination and laboratory investigations (ECG, CT scan, bone marrow aspiration, Echocardiography, and enzyme analysis) the child was diagnosed to have Classic infantile onset Pompe disease. The parents were explained about the treatment option, prognosis etc. The child was started with Myozyme treatment (imported from Germany) and is on regular enzyme replacement therapy. At present the child is two years old, weighing 7kg, achieving normal milestone for the age and leading a near normal life on an average.
| The Role of a Nurse as Care Coordinator|| |
Caring for a child with Pompe disease needs interdisciplinary approach. Apart from providing direct care to the child, the nurse plays an important role in coordinating the health care activities of other team members (see [Figure 2]). Care coordination of individuals with Pompe disease is essential to the support and treatment of patients and families which is mainly based on the individual needs. Local customs and financial requirements and other factors contribute to decisions of who assumes this role. Nurses, genetic counselors, local primary care provider, medical genetists, metabolic disease specialists, and neurologists may take a central role in culturally sensitive care. Social worker may also facilitate and coordinate some of these services (Kishnani et al., 2006).
|Figure 2: Coordinated services in the care of child with Pompe disease (Source: Genzyme, 2005)|
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| Roles and responsibilities of a nurse as health team coordinator or care coordinator|| |
The various roles and responsibilities of a nurse as a health team coordinator are summed up as follows :
- Recognizing that family is constant in a patient’s life, the plan of care should be centered on the needs identified by the family and health care providers working as a team
- Collaboration should be facilitated at all levels of care to allow for equal participation in establishing the goals of care
- Clear and prompt information about therapies, treatment and resources should be continuously shared with the family in an appropriate and supportive manner
- The support network for resources of information and financial management should be identified
- Collect comprehensive history regarding the onset of signs and symptoms, feeding pattern, growth and developmental milestones, and family history
- Administer medication - Myozyme 20mg/kg (each vial contains 50mg of Myozyme). The total dosage of drug should be dissolved in distilled water (50mg/10ml of water). Dilute the total dissolved solution in 0.9% Normal Saline at the ratio of 1:30. Then the drug should be infused through infusion pump starting with slow rate as prescribed by the pediatrician, doubling the rate of infusion in the 2nd hr. The total drug has to be administered for at least 4-5hrs and once in every three weeks
- Monitor vital parameters
- Monitor growth and developmental milestones periodically
- Provide genetic counseling to the family members.
- Explaining family inheritance patterns and identifying potentially at-risk individuals
- Providing balanced information about what genetic testing involves to support decisions about who to test
- Helping family members cope with positive test results
- Providing guidance on genetic issues such as family planning and prenatal testing
| Conclusion|| |
With invention of the enzyme therapy, children with Pompe disease can lead a near to optimal life. But the main obstacle is the financial resources. At present, this drug is not manufactured in India and must be imported based on the necessity. This may pose huge financial burden on the family welfare of those individuals with Pompe disease. Hence nurse plays a vital roles in the care of children with Pompe disease.
Conflicts of Interest: The author has declared no conflicts of interest.
| References|| |
Genzyme. (2005). A physician guide to Pompe disease
. Retrieved from www.worldpompe.org/…/8-for- physicians?…physician-s-guide-to-pomp…
Kishnani, P. S., Steiner, R. D., Bali, D., Berger, K., Byrne, B. J., Case, L. E., … Watson, M. S. (2006). Pompe disease diagnosis and management guideline. Genetics in Medicine
, 8(5), 267-288.
Kleigman, R. M., Stanton, B., Geme, J., Schor, N., & Behrman, R. E. (2012). Nelson’s textbook of pediatrics
. New Delhi. Elsevier publications.
National Institute of Neurological Disorders and Stroke. (2013). Pompe disease
. Retrieved from www.nind.nih. gov/ disorders/pompe/pompe.html
Wagner, K. R. (2007). Enzyme replacement for infantile Pompe disease: The first step toward a cure. Neurology
, 68(2), 88-89.
[Figure 1], [Figure 2]