Newborn Screening for Pompe Disease.

Area of Science:

• Genetics and Metabolic Disorders
• Newborn Screening Programs
• Enzyme Replacement Therapy

Background:

• Pompe disease (PD) is an inherited metabolic disorder caused by alpha-glucosidase (AαGlu) deficiency, leading to glycogen buildup in muscles.
• Early intervention with enzyme replacement therapy (ERT) is critical for improving outcomes in infantile-onset PD.
• Residual AαGlu enzyme activity dictates disease progression and treatment efficacy.

Purpose of the Study:

• To review the implementation and experiences of newborn screening (NBS) programs for Pompe disease globally.
• To highlight the importance of early diagnosis and treatment initiation for optimal PD management.
• To address challenges in NBS for PD, particularly the impact of pseudodeficiency alleles.

Main Methods:

• Measurement of AαGlu enzyme activity in dried blood spots (DBSs) using fluorometry, tandem mass spectrometry, or digital microfluidic fluorometry for NBS.
• Analysis of GAA gene mutations to complement NBS findings.
• Review of international NBS programs and their experiences with PD screening.

Main Results:

• Newborn screening allows for the early detection of PD, enabling timely initiation of ERT.
• Early ERT in infantile PD significantly improves survival, respiratory function, motor development, and quality of life.
• Pseudodeficiency alleles, common in Asian populations, complicate NBS interpretation and necessitate confirmatory genetic testing.

Conclusions:

• Newborn screening is the most effective strategy for early diagnosis and treatment of Pompe disease.
• Integrating GAA gene analysis with NBS is essential for accurate and definitive PD diagnosis.
• Continued development and refinement of NBS programs are vital for managing Pompe disease worldwide.