Managing Pompe disease
Pompe disease is a condition for which a specific treatment is available in many countries. The treatment is an enzyme replacement therapy (ERT) called alglucosidase alfa (Myozyme), manufactured by Sanofi Genzyme. Myozyme is indicated for long-term enzyme replacement therapy (ERT) in patients with a confirmed diagnosis of Pompe disease (acid alpha glucosidase deficiency). Myozyme is indicated in adults and paediatric patients of all ages.1
Guidelines for management
Although the underlying basis of Pompe disease is progressive muscular degeneration, the disease can affect different organs and systems. Patient care and management of this multisystemic disorder are thus best handled by a multidisciplinary team of healthcare providers.2
Multidisciplinary teams of specialist physicians in the USA have produced management guidelines, which have been approved by the American College of Medical Genetics (ACMG)2 and the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM):3
The progressive nature of Pompe disease, together with the unpredictable nature of that progression, means that regular patient monitoring is of paramount importance. Changes in a patient’s clinical status can then be identified without delay and their treatment/management plan adjusted accordingly 8.
All infants with Pompe disease must be monitored closely and frequently, given the rapid progression in this patient group. In older patients with a slower rate of progression, a general guideline is to follow-up every 6−12 months.2,3, A patient’s healthcare team will determine the exact nature and frequency of assessments according to individual clinical needs.
Pompe Registry assessment schedule
The Pompe Registry has developed a recommended schedule of assessments, based on input from international specialists with expertise in the care of patients with Pompe disease:
Areas of assessment
Key assessment areas when monitoring the manifestations and progression of Pompe disease are:2–5
Cardiac monitoring is critical for infants with Pompe disease, as most die from cardiac failure by age of 1 year without treatment. Chest x-rays and ECGs enable ongoing evaluation of cardiomyopathy progression, to guide treatment decisions. In severe cases, 24-hour ambulatory ECG may be useful to monitor increased risk of arrhythmia and sudden death.
Monitoring weight is important for all patients with Pompe disease. In infants, for example, this importance stems from the feeding difficulties that can make maintaining a healthy weight challenging. There are also a variety of recommended quality-of-life surveys and scales for patients, to help monitor disease progression and assess mental and emotional well-being.
Respiratory failure is the most common cause of death among children and adults with Pompe disease,4 even among those who have not been on artificial ventilation.5 Respiratory insufficiency is not always easily recognized, so use of routine testing of pulmonary function (including lung vital capacity and diaphragmatic strength) is crucial, even for patients without apparent signs, as an abrupt clinical decline can occur at any time. Detailed sleep history obtained at diagnosis and at follow-up visits can be helpful too, as sleep-disordered breathing is often an early manifestation of respiratory symptoms2. Practical Recommendations for Diagnosis and Management of Respiratory Muscle Weakness in Late-Onset Pompe Disease has been published by the Pompe Disease Respiratory CareWorking Group, an international group bringing together experts from various clinical disciplines 9.
Musculoskeletal and neurological
Musculoskeletal and neurological evaluations, including radiography, electromyography (EMG) and motor milestone benchmarks, help to evaluate and track patients’ functional and motor skills, as well as disease progression2. These are important tools for informing decisions about physical rehabilitation and other interventions. Testing for low bone mineral density may also be indicated, as this has been seen in patients of various ages.
The European Pompe Consortium (EPOC) agreed on a minimal dataset of outcome measures for adult patients and developed recommendations on start and stop criteria for ERT 8,10.
The multisystemic impact of Pompe disease is such that symptom management and supportive care fall into several categories.
Pompe disease results in progressive muscular degeneration, which causes varying types and degrees of physical disability. Management of these clinical manifestations is focused on preserving and improving physical function, as well as enhancing patient comfort. Equally important is alleviation or prevention of secondary complications, such as contracture, deformity and low bone mineral density.2Rehabilitation programs should be tailored to patients’ individual needs and may include a range of therapies and strategies, such as:2,3
- Physical therapy
- Occupational therapy
- Speech therapy
- Adaptive and assistive devices
- Orthopedic intervention and/or surgery
Respiratory support is one of the most critical forms of management, as most patients with Pompe disease experience some form of respiratory compromise, with respiratory failure being the most common cause of premature death among children and adults with the disease.3,5,9
Respiratory support often involves:
Use of supplemental oxygen (restricted to certain situations)
Airway secretion clearance through assistive cough and other techniques
Various forms of mechanical ventilation to assist weakened breathing muscles, with tracheostomy in the most severe cases
Feeding modifications to reduce aspiration risks
Up-to-date vaccinations, including vaccination against pneumococcus and influenza
Other interventions may include special forms of physical therapy to strengthen weakened respiratory muscles2, as well as aggressive management of infection. Generally, more frequent and invasive respiratory support is required as the disease progresses.6,7,9
Infants often require frequent cardiac assessment and management of symptoms. These patients are at risk of cardiomyopathy, cardiomegaly, congestive heart failure, arrhythmias, and cardiac arrest during surgery. Pharmacologic treatment should be based on the stage of cardiomyopathy.2
The need for any form of surgery in infants with Pompe disease should be carefully weighed against the significant risks of anesthesia in these patients. Therefore, anesthesia should be used only when absolutely necessary, and always overseen by an experienced pediatric and/or cardiac anesthetist. Recent data however suggest that with proper precautionary measures and a critical choice of timing of the operation, general anesthesia in children with Pompe disease could be relatively safe nowadays. 11
As a chronic, degenerative illness with profound effects on quality-of-life, Pompe disease can have a considerable emotional and psychological impact on patients and their families. An integral part of patient care is thus providing a range of psychosocial support services to help ease the burden and improve overall well-being:2,3
- Individual and family counseling
- Access to disease education
- Patient organizations and advocacy groups
- Support groups and networks for connecting with other patients
- Mental health and social work services
General medical care
Muscle weakness associated with Pompe disease, as well as respiratory and cardiac signs of the condition, can often compromise patients’ general health and well-being.2,3 For example, many individuals experience problems with mobility, an increased susceptibility to infections and difficulty maintaining weight. A variety of therapies and strategies can help to manage and control these issues:
- Dietary therapy and other techniques for ensuring adequate nutrition
- Taking special care with medications and their side effects, and following post-surgery recommendations
- Strategies to prevent and manage infections
1. Myozyme Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000636/WC500032125.pdf. Accessed March 2015.
2. Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guidelines. Genet Med 2006; 8:267-88.
3. Cupler EJ, Berger KI, Leshner RT, Wolfe GI, Han JJ, Barohn RJ, Kissel JT. AANEM Consensus Committee on Late-onset Pompe Disease. Consensus treatment recommendations for late-onset Pompe disease. Muscle Nerve. 2012
4. Hirschhorn R, Reuser AJ. Glycogen Storage Disease Type II: Acid α-Glucosidase (Acid Maltase) Deficiency. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G., eds. The Online Metabolic and Molecular Bases of Inherited Disease. OMMBID. Available at: http://ommbid.mhmedical.com/book.aspx?bookid=971. Accessed February 2015.
5. Winkel LP, Hagemans ML, van Doorn PA, et al. The natural course of non-classic Pompe’s disease; a review of 225 published cases. J Neurol 2006; 252:875-84.
6. Hagemans ML, Hop WC, Van Doorn PA, Reuser AJ, Van der Ploeg AT. Course of disability and respiratory function in untreated late-onset Pompe disease. Neurology 2006; 66:581-3.
7. Mellies U, Lofaso F. Pompe disease: A neuromuscular disease with respiratory muscle involvement. Respir Med. 2009;103(4):477-84
8. Van der Ploeg AT et al. European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: a 10-year experience. Eur. Journal of Neurology 2017; 0:1-14
9. Boentert et al, Practical Recommendations for Diagnosis and Management of Respiratory Muscle Weakness in Late-Onset Pompe Disease. Int. J. Mol. Sci. 2016, 17(10), 1735
10. Schoser et al, 208th ENMC International Workshop: Formation of a European Network to develop a European data sharing model and treatment guidelines for Pompe disease Naarden, The Netherlands, 26–28 September 2014. Neuromuscular Disorders 2015, Volume 25, Issue 8, Pages 674–678
11. Bosman et al, Perioperative management of children with glycogen storage disease type II-Pompe disease. Paediatr Anaesth. 2018 May;28(5):428-435. doi: 10.1111/pan.13361. Epub 2018 Mar 25
GZEMEA.PD.14.11.0313e(1) – February 2019