A large‐scale nationwide newborn screening program for pompe disease in Taiwan: Towards effective diagnosis and treatment

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.

LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population

“…So far, a large number of newborns have been screened for Pompe disease (over 400 000 infants). Of those screened, 6 infants were found to carry the infantile-onset Pompe disease (IOPD—prevalence 1/57 000), and 20 cases of LOPD and 294 cases of pseudodeficiency were also detected 14 15…”

Current status of newborn screening worldwide: 2015

“…The Japanese Ministry of Health and Welfare decided to expand publicly funded NBS to include inborn errors of amino acid, organic acid, and fatty acid metabolism in 2012, 150 but in most other Asian countries, patients must pay for this additional (optional) testing. There has also been increasing interest in NBS for LSDs, and significant progress with Pompe disease screening has been reported in Taiwan, [151][152][153] Japan, 154 and Korea. 155 Additional pilot studies in the region for other LSDs (Niemann-Pick A/B, Krabbe, Gaucher, Fabry, and Hurler syndrome) have been reported.…”

Newborn screening for lysosomal storage disorders

“…8,9,[22][23][24][25] In Taiwan, 2 NBS laboratories implemented a fluorometric assay for routine screening for Pompe disease but one switched to MS/MS in 2010. 25,26 The switch to MS/MS was possible because, in collaboration with Chamoles, Michael Gelb, C. Ronald Scott, and others developed enzyme-specific substrates, synthesized isotopically labeled substrates, and measured the products of various enzyme reactions simultaneously in DBS with MS/ MS. 27 Since the first description of their Flow Injection Analysis (FIA) MS/MS assay, modifications including the number of enzymes, sample preparation steps, and the addition of liquid chromatography (LC) have been reported and applied in both limited studies and routine NBS. [28][29][30][31][32][33][34][35][36][37][38][39] Another analytical multiplex approach to NBS for LSDs, also based on Chamoles' fluorometric enzyme activity assays, was developed by Advanced Liquid Logic, Inc. (ALL; now called Baebies Inc.).…”