Pompe disease

Disease Description (Causes and Symptoms)

• Definition summary: Pompe disease is an inherited metabolic disorder caused by a deficiency of acid alpha-glucosidase (GAA), an enzyme essential for glycogen breakdown within lysosomes, resulting in glycogen accumulation in lysosomes and involvement of the muscles (skeletal muscles and diaphragm) and heart.
• Cause: It is an autosomal recessive genetic disorder caused by a variant in the GAA gene. Clinical manifestations vary according to the degree of enzyme activity.
• Pathophysiology: GAA deficiency causes glycogen accumulation within lysosomes, leading to lysosomal enlargement and cellular damage → muscle fiber destruction, muscle weakness, and respiratory muscle weakness; in the infantile form, cardiomegaly, cardiomyopathy, and heart failure may occur.
• Main symptoms and clinical forms
  • Infantile form (severe form): Hypotonia, severe muscle weakness, macroglossia, cardiomegaly and cardiomyopathy (heart failure) within several months after birth; there is a high risk of death within 1 year due to rapid clinical deterioration.
  • Childhood form (moderate form): Onset during infancy or after school age, with delayed motor development and hypotonia; cardiomyopathy is rare, but there is a gradual risk of respiratory failure.
  • Adult form (mild or late-onset form): The main symptoms are slowly progressive skeletal muscle weakness during adolescence or adulthood (in the thighs, lower back, and spinal support muscles) and diaphragmatic weakness, causing gait disturbance, sleep apnea, and dyspnea. Cardiac involvement is rare.
• Diagnostic findings (summary): Reduced GAA enzyme activity (in fibroblasts, muscle tissue, or processed peripheral blood lymphocytes), confirmation of a GAA gene variant, lysosomal vacuoles and PAS-positive glycogen accumulation on muscle biopsy, and possible increases in CK and LDH.

Treatment Methods

• Definitive treatment
  • Enzyme replacement therapy (ERT): Alglucosidase alfa (e.g., Myozyme/alglucosidase alfa). Prolonged survival and improved muscle strength have been confirmed in the infantile form, and functional improvement has also been reported in the childhood and adult forms.
  • Gene therapy is in the research stage and is currently being investigated in some clinical trials.
• Symptomatic and supportive treatment
  • Respiratory management: Regular pulmonary function testing (especially FVC and the difference between upright and supine positions), nighttime sleep apnea testing (polysomnography), noninvasive ventilation when necessary (at night or continuously), and management of aspiration risk.
  • Cardiac management (mainly for the infantile form): Evaluation for heart failure and arrhythmias (electrocardiography and echocardiography); consultation with a cardiologist is necessary when medication treatment for heart failure is required.
  • Rehabilitation: Physical and occupational therapy to maintain muscle strength and preserve function, along with orthoses and walking aids.
  • Infection prevention: Vaccination, especially against influenza, and active treatment when an infection occurs.
  • Nutritional management: Nutritional counseling aimed at preserving muscle strength, such as a high-protein diet, with individual adjustments.
• Special precautions and management
  • Anesthesia risk: General anesthesia may worsen muscle weakness and respiratory failure → multidisciplinary evaluation before anesthesia and consultation with an anesthesiologist are essential.
  • Immune response: Antibodies to ERT may develop, particularly a high antibody response in CRIM-negative patients → antibody testing and immunomodulatory therapy, when necessary, should be considered.
  • Bone marrow transplantation: Generally ineffective.
• Recommended monitoring items (periodically)
  • Respiratory system: Airway pressure and spontaneous breathing capacity, FVC (in standing and supine positions), polysomnography when necessary
  • Heart: Electrocardiography and echocardiography (especially frequently in the infantile form)
  • Muscle function: 6-minute walk test (6MWT), muscle strength assessment, and activity measures
  • Laboratory tests: Markers of muscle injury such as CK and LDH, and ERT-related antibody testing
  • Genetics/family: Family testing and genetic counseling

Outpatient Visit Checklist (Including Sample Questions)

• Items to prepare and points to check
  • A list of all medications and supplements currently being taken (including doses and administration times)
  • Previous test records: GAA enzyme test results, GAA genetic test results (if already performed), echocardiography, electrocardiography, and pulmonary function test results, and recent blood test results (including CK)
  • A record of changes in current symptoms: Whether dyspnea is worsening (during exercise, at rest, or when lying down), sleep problems (snoring or suspected apnea during sleep), changes in walking ability, difficulty swallowing, and weight changes
  • Whether respiratory assistive devices are being used (oxygen, noninvasive ventilator, etc.)
  • Vaccination records (including influenza vaccination)
  • Recent infections or hospitalization history, scheduled surgery, and whether anesthesia will be required
• Materials useful to show the doctor during the outpatient visit
  • Recent pulmonary function test (PFT) results
  • Echocardiography and electrocardiography reports
  • Genetic test report, if available
  • Photos or videos showing walking status, if necessary

Examples of General Questions to Ask the Doctor

• "What are the expected effects and possible side effects of the enzyme replacement therapy I am receiving (or will receive)?"
• "What is the prognosis? If I receive treatment, what changes can be expected in daily functioning and survival?"
• "Are there any activities I should be especially careful about or any medications or situations I should avoid in daily life?"
• "Which vaccinations do you recommend to prevent infections? Is any special preparation needed for surgery or anesthesia?"
• "Which tests should I undergo regularly, and how often should they be performed?"

Examples of Disease-Specific Questions

• "What is the significance of my (or the patient's) GAA genetic test results (or enzyme activity level)? How is CRIM status (cross-reactive immunologic material positive/negative) determined, and how does it affect treatment selection?"
• "How do you monitor whether antibodies are forming during enzyme replacement therapy? If antibodies develop, how will the treatment plan change?"