A large-scale nationwide newborn screening program for Pompe disease in Taiwan: towards effective diagnosis and treatment.
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.
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
Chia-Feng
CF
Yang
Hao-Chuan
HC
Liu
Ting-Rong
TR
Hsu
Fang-Chih
FC
Tsai
Sheng-Fong
SF
Chiang
Chuan-Chi
CC
Chiang
Hui-Chen
HC
Ho
Chih-Jou
CJ
Lai
Tsui-Feng
TF
Yang
Sung-Yin
SY
Chuang
Ching-Yuang
CY
Lin
Dau-Ming
DM
Niu
D000465:Algorithms; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis* / Q000453:epidemiology* / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008403:Mass Screening; D009313:National Health Programs; D015997:Neonatal Screening; D013624:Taiwan / Q000453:epidemiology; D000520:alpha-Glucosidases / Q000097:blood / Q000235:genetics
D000520:alpha-Glucosidases
acid α-glucosidase; enzyme replacement therapy; infantile-onset Pompe disease; newborn screening