Newborn Screening for Pompe Disease

Abstract

Glycogen storage disease type II (also known as Pompe disease (PD)) is an autosomal recessive disorder caused by defects in α-glucosidase (AαGlu), resulting in lysosomal glycogen accumulation in skeletal and heart muscles. Accumulation and tissue damage rates depend on residual enzyme activity. Enzyme replacement therapy (ERT) should be started before symptoms are apparent in order to achieve optimal outcomes. Early initiation of ERT in infantile-onset PD improves survival, reduces the need for ventilation, results in earlier independent walking, and enhances patient quality of life. Newborn screening (NBS) is the optimal approach for early diagnosis and treatment of PD. In NBS for PD, measurement of AαGlu enzyme activity in dried blood spots (DBSs) is conducted using fluorometry, tandem mass spectrometry, or digital microfluidic fluorometry. The presence of pseudodeficiency alleles, which are frequent in Asian populations, interferes with NBS for PD, and current NBS systems cannot discriminate between pseudodeficiency and cases with PD or potential PD. The combination of GAA gene analysis with NBS is essential for definitive diagnoses of PD. In this review, we introduce our experiences and discuss NBS programs for PD implemented in various countries.

Molecular Diagnosis of Pompe Disease in the Genomic Era: Correlation with Acid Alpha-Glucosidase Activity in Dried Blood Spots

“…Measurement of acid alpha-glucosidase activity on dried blood spots is used fo born screening and has also been used widely in "high-risk" populations to scre Pompe disease [11,12,21]. Although it is an efficient and low-cost approach to id…”

“…Measurement of acid alpha-glucosidase activity on dried blood spots is used for newborn screening and has also been used widely in "high-risk" populations to screen for Pompe disease [11,12,21]. Although it is an efficient and low-cost approach to identify potential cases of Pompe disease, putative positive cases require confirmation by mutation analysis and exclusion of pseudodeficiency alleles [22].…”

“…A single LOPD patient presented only with unexplained respiratory insufficiency and showed normal CK levels and EMG. Among all patients with available CK data (12), only one patient (LOPD) had normal CK at the time of diagnosis.…”

“…In that context, newborn screening was proposed to enable early diagnosis. Several pilot studies subsequently demonstrated its favorable impact on patient outcomes, leading to the introduction of population newborn screening for Pompe disease of 11 in some jurisdictions [11,12]. To provide a low-cost and rapid screening test, dried blood spots (DBS) are used to measure acid alpha-glucosidase enzymatic activity, by fluorometric assays or by tandem mass spectrometry [11,13].…”

Advanced Diagnostic System and Introduction of Newborn Screening of Adrenoleukodystrophy and Peroxisomal Disorders in Japan

“…Furthermore, newborn screening for several intractable diseases in which early diagnosis and treatment may be the optimal approach have already been performed in some groups in Japan, in addition to these 20 diseases. For example, a group at Kumamoto University has been undertaking newborn screening for lysosomal storage disorders, including Fabry disease, Pompe disease, Gaucher disease, and mucopolysaccharidosis type I and II since 2006 [14,15].…”