Management of Infantile-Onset Pompe Disease

A multidisciplinary approach is needed due to the complex and multisystemic basis of infantile-onset Pompe disease (IOPD).

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, cardiology, neuromuscular specialist, and physical & occupational therapy.

Figure 1. Ongoing monitoring through assessments and management of symptoms are critical to an infantile-onset Pompe disease (IOPD) patient’s care plan.

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.

This schedule of assessments contains recommendations for those less than 5 years of age, with attention to IOPD where appropriate.

Supported by the standard-of-care guidelines published by the American College of Medical Genetics and other resources, these assessments monitor cardiac involvement, respiration, gastrointestinal involvement, hearing, motor development, and cognition in addition to laboratory and general assessments.

Management of IOPD involves supportive therapies focused on each patient's individual symptoms. Optimal management of IOPD symptoms requires a multidisciplinary approach and can comprise cardiac care, respiratory support, rehabilitation therapy, psychosocial support, and general care domains as needed.

Cardiac Care

Especially in classic IOPD, infants require frequent cardiac assessment and management of symptoms with consultation of a pediatric cardiologist. Use of pharmacological treatment can ease symptoms of cardiomyopathy, but stage of the disease will dictate the pharmacology used.

Arrhythmias (eg, tachydysrhythmias of Wolff-Parkinson-White syndrome ) with risk of sudden death have been reported in IOPD, emphasizing the need to avoid hypotensive states brought on by general anesthesia and drugs such as β–blockers.

Respiratory Support

Respiratory support is one of the most critical forms of IOPD management because most patients experience some form of respiratory compromise and respiratory failure is the most common cause of premature death among children and adult patients.

Respiratory therapy most often involves

  • Various forms of mechanical ventilation to assist weakened breathing muscles
  • Use of supplemental oxygen (restricted to certain situations)
  • Airway secretion clearance
  • Tracheostomy in the most severe cases
  • Feeding modifications to reduce aspiration risks

Other interventions may include special forms of physical therapy to strengthen weakened respiratory muscles as well as aggressive management of infection.

Mechanical Ventilation

Progressive Ventilatory Support

Mechanical ventilation can help prolong survival in patients with acute respiratory failure as well as ease respiratory symptoms in less severely affected patients. The progressive nature of Pompe disease generally results in an increased dependence on ventilation over time.

Patients with IOPD can progress very rapidly and can require ventilation and permanently depend on it within the first few months of diagnosis.

Modes of Ventilation

In earlier stages of the disease, noninvasive ventilation is often sufficient (with or without supplemental oxygen as indicated):

  • Nasal continuous positive airway pressure ventilators are recommended for obstructive sleep apnea
  • Bilevel airway pressure ventilators are recommended for nocturnal or daytime hypoventilation

In advanced cases in which a patient needs 24-hour ventilatory support, a tracheostomy may be necessary.

Secretion Clearance and Infection Management

Because of diaphragmatic and other respiratory muscle weakness, patients with IOPD have a weakened cough, resulting in retained pulmonary secretions and an increased risk of pneumonia and other infections.

Several therapies can help manage these complications and improve pulmonary function:

  • Mechanical cough-assistive devices
  • Manual measures such as suctioning and chest percussion
  • Prompt and aggressive treatment of pulmonary infection

Rehabilitation Therapy

Progressive muscular degeneration in IOPD can cause varying types and degrees of physical disability in addition to delayed motor development. Management of these clinical manifestations focuses on preserving and improving physical function as well as patient comfort. Equally important is alleviating or preventing secondary complications such as contracture, deformity, and low bone mineral density.

A rehabilitation program may be tailored to each patient’s needs and include a range of therapies and strategies such as

  • Physical therapy
  • Occupational therapy
  • Speech therapy
  • Adaptive and assistive devices

Physical Therapy

A customized physical therapy program for patients with Pompe disease may include exercises to help strengthen weakened muscles, improve range of motion, and develop motor skills.

A primary goal of physical therapy is to maximize the patient’s independence by improving mobility and general motor skills. Specific strengthening exercises can also target respiratory muscles to help maintain respiratory function. In addition, exercises designed to improve the function of muscles involved in chewing and swallowing may be employed to help with feeding difficulties.

Gentle stretching may also give symptomatic relief of contractures, scoliosis, and bone deformities, although in severe cases corrective orthopedic surgery may be necessary.

Speech Therapy

Patients with weakened facial and oral muscles may require speech therapy and other associated forms of intervention. This is especially needed in cases of hearing loss because speech and language development can be altered in patients with IOPD.

Occupational Therapy

Occupational therapy is important to help IOPD patients and caregivers learn new ways to complete daily tasks and adapt to their environments at home and, eventually, school.

Adaptive and Assistive Devices

Assistive devices in IOPD patient population may still be necessary. The progressive nature of Pompe disease and its impact particularly on proximal muscles means that many patients may need to rely on mobility devices. Patients with IOPD may remain non-ambulatory and eventually require wheelchairs.

Psychosocial Support

Infantile-onset Pompe disease is a chronic, degenerative illness that can have profound effects on the quality of life for both infants and their caregivers and cause considerable emotional and psychological impact. An integral part of patient care is providing a range of psychosocial support services to help ease the burden and improve overall patient well-being:

  • Individual and family counseling
  • Access to disease education
  • Patient organizations and advocacy groups
  • Support groups and networks for connecting with other patients

General Medical Care

Muscle weakness, as well as respiratory and cardiac signs, associated with IOPD can often compromise patients’ general health and well-being. For example, many infants with IOPD have an increased susceptibility to infections as well as difficulties maintaining weight. A variety of therapies and strategies can help manage and control these issues.

Nutrition and Weight Maintenance

Because of weakened facial and oral muscles, infants experience difficulties eating. Trouble with sucking, chewing, and/or swallowing can lead to insufficient caloric intake, problems maintaining a healthy weight, and a general failure to thrive. Inadequate nutrition may even lead to endogenous muscle protein breakdown:

Several approaches can help address these issues:

  • Physical therapy to help strengthen muscles and allow for independent feeding
  • Modification of food texture to facilitate swallowing and reduce the risk of aspiration
  • Carefully balanced diets to maximize nutrients and provide protein to muscles
  • Tube feeding (most common in severely ill infants)

Medical and Surgical Considerations

The cardiomyopathy found in classic IOPD, and potentially non-classic IOPD, requires careful consideration if any kind of surgery is required because use of anesthesia poses risks of arrhythmia and other cardiac events. Anesthesia may be used only when absolutely necessary and always overseen by cardiac anesthesiologists experienced in anesthetizing infants.

Preventing and Managing Infection

Because most patients with Pompe disease have some degree of respiratory impairment, they are often highly susceptible to pneumonia, bronchitis, and other infections, with infants particularly at risk for aspiration pneumonia.

Several important measures can help prevent these complications:

  • Routine immunizations including influenza, respiratory syncytial virus, and pneumococcal vaccines for patients and their household members
  • Strict handwashing precautions
  • Prompt medical attention of seemingly minor symptoms (like coughs or fever) that could indicate a more serious underlying condition
  • Aggressive treatment of infection to prevent progression to a more serious stage