Newborn Screening for Pompe Disease

Int J Neonatal Screen. 2020 Apr 5;6(2):31. doi: 10.3390/ijns6020031. eCollection 2020 Jun.

PMID: 33073027

Takaaki Sawada, Jun Kido, Kimitoshi Nakamura

Summary: Newborn screening (NBS) is the most effective method for detecting and treating Pompe Disease (PD) early on. On the other hand, current NBS systems are unable to distinguish between pseudodeficiency and cases with PD or potential PD. Therefore, a combination of GAA gene analysis with NBS is needed for definitive PD diagnoses.

Abstract

Background: Glycogen storage disease type II (also known as Pompe disease (PD)) is an autosomal recessive disorder caused by lysosomal glycogen accumulation in skeletal and heart muscles due to defects in alpha-glucosidase (A-α-Glu). The rate of accumulation and tissue damage is determined by the amount of residual enzyme activity. For achieving optimal outcomes, enzyme replacement therapy (ERT) should be begun before symptoms appear. Early ERT treatment increases survival, decreases the need for ventilation, leads to earlier independent walking, and improves patient quality of life in infantile-onset PD. 

Objective: Newborn screening (NBS) is the most effective method for detecting and treating PD early on. Fluorometry, tandem mass spectrometry, or digital microfluidic fluorometry are used in NBS for PD to measure A-α-Glu enzyme activity in dried blood spots (DBSs). The presence of pseudodeficiency alleles, which are common in Asian populations, interferes with NBS for PD, and existing NBS systems are unable to distinguish between pseudodeficiency and cases with PD or potential PD. 

Conclusion: For definitive PD diagnoses, a combination of GAA gene analysis with NBS is needed. The experiences of the authors are described and NBS programs for PD that have been implemented in different countries are discussed in this review.

Keywords: Pompe disease; genotype-phenotype correlation; newborn screening; pseudodeficiency; treatment and follow-up.