Early detection of Pompe disease by newborn screening is feasible: results from the Taiwan screening program
Yin-Hsiu Chien1, Shu-Chuan Chiang, Xiaokui Kate Zhang
1Department of Pediatrics, National Taiwan University Hospital, National Taiwan University School of Medicine, Taipei, Taiwan.
Insights
Newborn screening for Pompe disease in Taiwan is feasible. This pilot program enabled earlier diagnosis, allowing for timely assessment of enzyme replacement therapy benefits in infants.
Area of Science:
- Genetics and Genetic Diseases
- Metabolic Disorders
- Newborn Screening
Background:
- Pompe disease is a severe, progressive lysosomal storage disorder caused by acid alpha-glucosidase deficiency.
- Early enzyme replacement therapy (ERT) with alglucosidase alpha improves outcomes, particularly motor function.
- Timely diagnosis is crucial for initiating ERT during the critical early window.
Purpose of the Study:
- To evaluate the feasibility of a large-scale newborn screening program for Pompe disease in Taiwan.
- To utilize a fluorometric enzymatic assay on dried blood spots for acid alpha-glucosidase activity measurement.
- To establish an early diagnostic pathway for Pompe disease in newborns.
Main Methods:
- A pilot newborn screening program was conducted from October 2005 to March 2007.
- Dried blood spots from approximately 45% of Taiwanese newborns were analyzed for acid alpha-glucosidase activity.
- An unscreened population served as a control group for comparison.
Main Results:
- Over 132,000 newborns were screened, with a recall rate of 0.091%.
- Pompe disease was confirmed in 4 newborns through screening, comparable to the control group.
- Newborn screening facilitated significantly earlier diagnosis ( <1 month) compared to the control group (3-6 months).
Conclusions:
- This study demonstrates the feasibility of large-scale newborn screening for Pompe disease.
- Newborn screening enables earlier diagnosis, paving the way for evaluating early intervention strategies.
- Implementing newborn screening can improve the management and long-term prognosis of Pompe disease.
Objective:
Pompe disease is an autosomal recessive lysosomal storage disorder that is caused by deficient acid alpha-glucosidase activity and results in progressive, debilitating, and often life-threatening symptoms involving the musculoskeletal, respiratory, and cardiac systems. Recently, enzyme replacement therapy with alglucosidase alpha has become possible, but the best outcomes in motor function have been achieved when treatment was initiated early. The aim of this study was to test the feasibility of screening newborns in Taiwan for Pompe disease by using a fluorometric enzymatic assay to determine acid alpha-glucosidase activity in dried blood spots.
Methods:
We conducted a large-scale newborn screening pilot program between October 2005 and March 2007. The screening involved measuring acid alpha-glucosidase activity in dried blood spots of approximately 45% of newborns in Taiwan. The unscreened population was monitored as a control.
Results:
Of the 132 538 newborns screened, 1093 (0.82%) repeat dried blood-spot samples were requested and retested, and 121 (0.091%) newborns were recalled for additional evaluation. Pompe disease was confirmed in 4 newborns. This number was similar to the number of infants who received a diagnosis of Pompe disease in the control group (n = 3); however, newborn screening resulted in an earlier diagnosis of Pompe disease: patients were <1 month old compared with 3 to 6 months old in the control group.
Conclusions:
To our knowledge, this is the first large-scale study to show that newborn screening for Pompe disease is feasible. Newborn screening allows for earlier diagnosis of Pompe disease and, thus, for assessment of the value of an earlier start of treatment.
