Enzyme replacement therapy for infantile-onset Pompe disease

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Infantile-onset Pompe disease is a rare, progressive genetic disorder caused by acid alpha-glucosidase (GAA) deficiency.
• Current treatments include enzyme replacement therapy (ERT) with alglucosidase alfa and supportive care.
• CRIM-negative patients require immunomodulation before ERT.

Purpose of the Study:

• To assess the effectiveness, safety, and optimal dosage regimen of ERT for infantile-onset Pompe disease.
• To evaluate alglucosidase alfa dosing for this rare condition.

Main Methods:

• Searched multiple databases (Cochrane, PubMed, Embase) and clinical trial registries for relevant trials.
• Included randomized and quasi-randomized controlled trials in children with infantile-onset Pompe disease.
• Two authors independently selected trials, assessed bias, and extracted data.

Main Results:

• No trials compared ERT to placebo or other interventions.
• One small trial (18 participants) compared alglucosidase alfa doses (20 mg/kg vs. 40 mg/kg every two weeks) with low-quality evidence.
• Both doses showed similar clinical responses (cardiac, motor, ventilation-free survival) and infusion-related events, but long-term survival and cardiomyopathy improvement were noted.

Conclusions:

• No robust evidence exists to determine the most effective alglucosidase alfa dosing schedule.
• Ethical considerations preclude placebo-controlled trials; a large-scale RCT comparing different ERT doses is recommended.
• Standardization of clinical outcome reporting (cardiac function, motor development, survival, adverse events) is crucial.