Type II Glycogen Storage Disease (Pompe Disease) Treatment & Management

Unfortunately, no cure exists. However, Pompe disease has benefited from the introduction of enzyme replacement therapy (ERT), which, although expensive, is a major therapeutic advance. ERT benefits are attenuated by antibody formation, which has led to interest in combining ERT with immune modulation. 

Enzyme replacement therapy

The US Food and Drug Administration (FDA) has approved several enzymes that provide an exogenous source of the lysosomal enzyme acid alpha-glucosidase (GGA), which is deficient in Pompe disease. Enzyme replacement available in the United States includes the following:

• Avalglucosidase alfa (Nexviazyme): Indicated for treatment of patients aged 1 year and older with late-onset Pompe disease.
• Alglucosidase alfa (Myozyme): Shown to improve ventilator-free survival in patients with infantile-onset Pompe disease compared with untreated historical controls. It has not been adequately studied for treatment of other forms of Pompe disease.  
• Alglucosidase alfa (Lumizyme): Indicated for infantile-onset Pompe disease and also for late (non-infantile) Pompe disease. 
• Cipaglucosidase alfa IV (Pombiliti) in combination with oral miglustat (specifically, Opfolda): Indicated in adults with late-onset Pompe disease who are failing to improve on their current enzyme replacement therapy.

The design of cipaglucosidase alfa, a recombinant human alpha-glucosidase enzyme, enables the drug’s increased uptake into muscle cells. Inside the cell, cipaglucosidase alfa, after being processed into its most active and mature form, breaks down glycogen. Miglustat, an enzyme stabilizer, stabilizes the enzyme in the blood.

Approval of cipaglucosidase alfa, in 2023, was based on results from the phase 3, multicenter PROPEL study, in which randomized patients received either cipaglucosidase alfa (20 mg/kg IV) plus oral miglustat or alglucosidase alfa (20 mg/kg IV) plus oral placebo, once every 2 weeks. At week 52, neither group had attained statistical superiority over the other regarding improvement in 6-minute walk distance. Ongoing studies are assessing cipaglucosidase alfa’s long-term efficacy and its use in infantile Pompe disease. ^[15]

Other therapies

Respiratory toilet is important in non-infantile cases.

In some patients, liver transplantation may abolish biochemical abnormalities.

In 2000, Zingone and colleagues demonstrated the abolition of the murine clinical manifestations of Von Gierke disease with a recombinant adenoviral vector. ^[16] These findings suggest that corrective gene therapy for GSDs may be possible in humans.

Diet

In some cases, dietary therapy is helpful. Meticulous adherence to a dietary regimen may reduce liver size, prevent hypoglycemia, allow for reduction in symptoms, and allow for growth and development. A high-protein diet may be beneficial in the noninfantile form.

A high-protein diet consisting of 20-25% protein may provide increased muscle function in cases of weakness or exercise intolerance. In particular, a high-protein diet containing branched chain amino acids may slow or arrest disease progression.

Consultations

As Pompe disease is a multisystem disorder, a multidisciplinary approach is required. Team members should include specialists in the fields of neurology, pulmonology, general medicine (internal medicine, pediatrics, metabolism), cardiology, occupational therapists, and disease geneticists. A genetic counselor can determine risk to future offspring. ^[17]  

As Pompe disease is genetically inherited in an autosomal recessive pattern, it cannot be prevented if disease-causing mutations have not been identified in family members. Genetic counselors can educate families about the disease's inheritance patterns and risks, as well as support them through testing and family-planning decisions. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are appropriate when the mutations have been already identified in the family. The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy

Phupong and Shotelersuk describe prenatal electron microscopy of skin fibroblasts to exclude Pompe disease in the fetus. ^[18]

Some of the recommendations for monitoring are as follows ^[19] :

Cardiology recommendations 

• Obtain a chest radiograph at regular intervals

• Obtain an echocardiogram at regular intervals to evaluate the extent of cardiomyopathy

• Obtain a 24-hour ambulatory ECG at baseline and at regular intervals, as patients are at risk for life-threatening arrhythmias, including patients on enzyme replacement therapy

Pulmonary recommendations 

• Clinical assessment of respiratory status, both asleep and awake, should be performed at each medical visit

• Pulmonary function must be assessed annually or with changes in patients’ clinical condition

•  When clinically indicated, chest radiographs and polymnography must be obtained

• Maximizing clearance of airway secretions should routinely be performed

• Assessment of respiratory function during sleep needs to be made whenever the patient complains of daytime sleepiness or unexplained fatigue or has observed apneas during sleep, or when vital capacity falls below 40–50% predicted

• All pulmonary infections should be aggressively managed

Gastrointestinal recommendations

• Obtain videofluoroscopic swallowing assessment and evaluation for gastroesophageal reflux to guide management of feeding (oral/gavage feeding) as clinically indicated

• Provide oral stimulation and non-nutritive sucking for infants who are nonoral feeders

• Monitor growth parameters carefully

Musculoskeletal recommendations

• Screen for osteopenia/osteoporosis with dual-energy x-ray absorptiometry (DEXA) and follow up as needed

• Assess musculoskeletal impairments, functional deficits, levels of disability, and societal participation at regular intervals and as needed, including radiographs as needed for monitoring of scoliosis, hip stability, and long bone integrity

• Enhance muscle function by providing practice, movement, and gentle strengthening within limits of physiological stability by following guidelines for strengthening muscles from other progressive muscle disease

• Prevent and minimize contracture and deformity