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A large-scale nationwide newborn screening program for Pompe disease in Taiwan: towards effective diagnosis and
Chia-Feng Yang1, Hao-Chuan Liu, Ting-Rong Hsu
1Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
Insights
Newborn screening for Pompe disease identified infantile-onset Pompe disease (IOPD) through low enzyme activity, high creatine kinase, and enlarged heart measurements. Early diagnosis and enzyme replacement therapy (ERT) significantly improved outcomes for affected infants.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Pompe disease is a rare genetic disorder affecting muscle function.
- Infantile-onset Pompe disease (IOPD) requires early diagnosis and intervention for better outcomes.
- Newborn screening programs are crucial for identifying at-risk infants.
Purpose of the Study:
- To analyze results from a large-scale newborn screening for Pompe disease.
- To establish an effective diagnostic protocol for immediate IOPD diagnosis.
- To promote earlier treatment and improved outcomes for infants with IOPD.
Main Methods:
- Screened 402,281 newborns for Pompe disease.
- Referred infants with low acid α-glucosidase (GAA) activity for diagnostic confirmation.
- Utilized physical examination, biochemical markers (CK, liver enzymes), and echocardiograms for differentiation.
Main Results:
- Six infants were diagnosed with IOPD, all presenting with hypotonia, very low GAA activity, high CK, and high left ventricular mass index (LVMI).
- The diagnostic protocol effectively differentiated IOPD from late-onset Pompe disease and false positives.
- Five infants received enzyme replacement therapy (ERT) within 4 hours of admission, showing marked improvement.
Conclusions:
- Specific clinical indicators (hypotonia, high CK, enlarged LVMI, low GAA activity) enable rapid IOPD differentiation.
- Early differentiation facilitates prompt ERT initiation.
- Early ERT application in IOPD leads to significantly better patient outcomes.
Abstract:
The aim of this study was to: (a) analyze the results of a large-scale newborn screening program for Pompe disease, and (b) establish an effective diagnostic protocol to obtain immediate, valid diagnosis of infantile-onset Pompe disease (IOPD) to promote earlier treatment and better outcomes. In this study, 402,281 newborns were screened for Pompe disease from January 1, 2008 to May 1, 2012. Infants with low acid α-glucosidase (GAA) activity were referred to Taipei Veterans General Hospital for diagnostic confirmation. Physical examination, biochemical parameter (creatine kinase [CK], alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase), and echocardiogram assessments were performed immediately to effectively differentiate IOPD from suspected late-onset Pompe disease (LOPD) or false-positive cases with pseudodeficiency mutation. Six infants with IOPD all presented with hypotonia, extremely low GAA enzyme activity (≤0.5 µmol/L/hr) in initial dried blood spot analysis, high CK (≥250 U/L), and high left ventricular mass index (LVMI, ≥80 g/m(2)). By analyzing these parameters, IOPD was distinguished effectively and immediately from suspected LOPD and false-positive cases. Except for the first referred case, five of the infants with IOPD received first-time enzyme replacement therapy (ERT) within 4 hr of admission and exhibited marked improvement. Our findings indicate that certain clinical manifestations (hypotonia, high CK, enlarged LVMI, and extremely low GAA enzyme activity in initial dried blood spot analysis) can help in the rapid and effective differentiation of patients with IOPD from other patient with low GAA activity. Such differentiation allows for the early application of first-time ERT and leads to better outcomes.
