Managing Late-Onset Pompe Disease

Management of late-onset Pompe disease (LOPD) requires close surveillance and regular follow-up. Because of the multisystemic nature of LOPD, patients are best followed by a multidisciplinary team headed by a physician with experience managing Pompe disease or similar disorders. Members of the team may include the following specialists dictated by the major disease manifestations:

  • Metabolic disease specialist/ Biochemical geneticist
  • Pulmonologist
  • Neurologist
  • Neuromuscular specialist
  • Orthopedist
  • Cardiologist
  • Respiratory therapist
  • Physical therapist
  • Occupational therapist
  • Speech therapist
  • Otolaryngologist
  • Audiologist
  • Genetic counselor
  • Metabolic dietian
  • Pharmacist

Because the volume of appointments can become overwhelming to any patient, one of the team members should be available to help with coordination of the patient’s care plan.

Developing a Management Plan

It is important to remember that the care plan will differ for each patient will differ and will evolve over the course of a patient's life. An individual’s care plan will depend on their signs and symptoms and degree of clinical severity. Because of the progressive nature of Pompe disease, a patient’s management plan may require additional intervention at later stages of the disease course.

Management Guidelines and a Multidisciplinary Approach

Standard-of-care guidelines published by the American College of Medical Genetics is a resource for physicians and other healthcare providers caring for patients with Pompe disease (infantile-onset and late-onset).

As mentioned, a multidisciplinary approach is needed due to the complex and multisystemic basis of the disease. Not all members of the care team may be necessary at all times during the course of the disease but should be available should the need arise. Figure 1 is a schematic of the complexity of the care team and the importance of having 1 team member available to coordinate patient care.

This figure displays the care team for infantile-onset Pompe disease with a care coordinator helping to coordinate respiratory therapy, genetic counseling, nutrition & dietary therapy, speech therapy, psychosocial therapy,  physical therapy and occupational therapy.

Figure 1. Examples of some possible Pompe disease multidisciplinary care team members

Symptom Management

Optimal care of a patient with LOPD falls into a variety of categories due to the diverse range of symptoms. Below is a synopsis of the different categories of care a patient with LOPD may require and their associated management methodologies. It is a topline summary of management based on the most common symptoms and is not meant to be a comprehensive list. For additional information regarding the most current recommendations, please refer to the management guidelines.

Respiratory muscle weakness is very common in patients with LOPD, affecting up to 80% of patients, and involves both inspiratory and expiratory musculature. Initial symptoms of respiratory insufficiency, including morning headaches, daytime fatigue, nocturnal hypoventilation, and sleep-disordered breathing, may be managed with non-invasive respiratory support methods. These can include:

  • Inspiratory muscle training
  • Cough assist devices
  • Airway clearance
  • Supplemental O2
  • BiPAP/CPAP
  • Bronchodilators

As the disease progresses, respiratory symptoms may continue to get worse. Indeed, respiratory failure is the most common form of death in LOPD patients. Pulmonary infections should, at best, be avoided and aggressively treated. If hypoventilation is present during sleep and waking hours, tracheostomy tube placement and mechanical ventilation could be considered.

Progressive muscle weakness is a hallmark of Pompe disease due to the accumulation of glycogen in skeletal muscles. This manifests as decreased motor function, altered postural tendencies and positioning, as well as the use of compensatory patterns of movement. Other musculoskeletal pathologies that can affect movement and function include contracture, osteoporosis, and deformity. Patients with LOPD may also suffer from bulbar muscle weakness, subsequent dysarthria, and occasionally dysphagia.

Rehabilitative services available for patients with LOPD may be comprehensive and include:

  • Physical therapy
  • Occupational therapy
  • Speech therapy
  • Assistive technology
  • Educational/vocational rehabiliation
  • Respiratory therapy
  • Orthopedics
  • Independent living services
  • Adaptive equipment/ orthotic intervention

The goals of physical therapy may include:

  • Optimization and preservation of physical function
  • Prevantion of secondary complications
  • Promotion and maintainance of maximal function

Many options are available to assist patients with LOPD with physical functioning, such as bathing/grooming, sitting, standing, sleeping, and general mobility.

Being diagnosed with a chronic, progressively degenerative disease profoundly affects patients and those who care for them. Every aspect of daily living that is routine for most others becomes a task that gets increasingly more difficult for an LOPD patient. Although the future is not guaranteed for anyone, most people can look ahead with a reasonable semblance of optimism. Patients with LOPD know that the road ahead will become increasingly more difficult. However, living with LOPD need not mean a patient give up. Indeed, many patients are able to take care of themselves, take advantage of resources and help available to them, and thrive. Nonetheless, it is paramount that patients and their families and caregivers have access to a range of psychosocial support services that can include:

  • Individual/family counseling
  • Patient support groups
  • Patient organization/ advocacy groups
  • Disease education
  • Genetic counseling

A reasonable concern for adult patients with LOPD may be the subject of intimacy, pregnancy, and having children. Genetic counseling can benefit families to discuss diagnosis and anticipatory management.

Because most patients with Pompe disease have some degree of respiratory impairment, they are often highly susceptible to pneumonia, bronchitis, and other infections. Inspiratory and expiratory muscles (abdominal and intercostals) are used for effective coughing, and many patients with Pompe disease may have trouble clearing airway secretions and mucus after an infection or surgery.

Several important measures can help prevent these complications:

  • Adults with LOPD may receive vaccinations for influenza and pneumococcal pneumonia, especially in the winter months
    • Pay special attention to symptoms (even seemingly minor ones) indicative of infection
    • Employ aggressive management as early as possible
    • Family members living with the LOPD patient may receive the influenza vaccine during flu season
  • The patient and family members/caregivers may follow strict hand-washing precautions and basic rules of hygiene to avoid potential infections
  • Surgery requiring anesthesia presents unique challenges to any Pompe patient; in LOPD, considerations may be taken for the following:
    • Patients with advanced muscle weakness may be more sensitive to neuromuscular blocking agents due to the potential for life-threatening or fatal hyperkalemia
    • Post-surgical cough insufficiency or hypoventilation due to diaphragm weakness may be monitored
    • Take precautions for the risk of malignant hyperthermia

Ongoing Monitoring

Because of the progressive nature of Pompe disease and the unpredictable nature of that progression, regular patient monitoring is important to identify changes in clinical status and adjust the management plan accordingly.

In LOPD patients with a variable degree of progression, a general guideline is to follow up every 6 months. Please note that the patient’s healthcare team may determine the frequency of assessments necessary according to individual patient needs.

In general, the healthcare team may perform the following main areas of assessment on a regular basis:

Quality of life (QoL): A variety of QoL questionnaires, surveys, and scales are available to assess a patient’s perception of their family/work/home life. Reductions in QoL require inquiry into the necessity for further evaluation or some form of social support.

Musculoskeletal and neurologic: Osteoporosis and osteopenia are being recognized as emerging issues in Pompe patients of all ages and indicate the importance of screening. Dual energy x-ray absorptiometry, or DEXA, may be performed at regular intervals but not more frequently than every 6 months. Musculoskeletal strength or impairment may be assessed regularly or as needed and can include x-rays to monitor for hip stability and long bone integrity.

Respiratory: Routine assessment of pulmonary function is of vital importance because respiratory failure is the leading cause of death in LOPD patients. Pulmonary function/gas exchange may be assessed annually or at every visit, or upon change in clinical status. Chest x-rays may be obtained upon diagnosis and when indicated. Sleep study tests may be obtained when clinically indicated (ie, when the patient complains of daytime sleepiness or unexplained fatigue, has observed sleep apneas, or vital capacity falls below 40%–50% predicted value).

Scheduling of Assessments

The Pompe Registry has developed a recommended schedule of assessments, based on the input of physicians from the international medical community with expertise in the care of patients with Pompe disease.