The Timely Needs for Infantile Onset Pompe Disease Newborn Screening-Practice in Taiwan.

Shu-Chuan Chiang,Wuh-Liang Hwu,Ni-Chung Lee,Yin-Hsiu Chien,Kai-Ling Chang

doi:10.3390/ijns6020030

Shu-Chuan Chiang, Wuh-Liang Hwu + Show 3 more

Open Access

https://doi.org/10.3390/ijns6020030

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Abstract

Pompe disease Newborn screening (NBS) aims at diagnosing patients with infantile-onset Pompe disease (IOPD) early enough so a timely treatment can be instituted. Since 2015, the National Taiwan University NBS Center has changed the method for Pompe disease NBS from fluorometric assay to tandem mass assay. From 2016 to 2019, 14 newborns were reported as high-risk for Pompe disease at a median age of 9 days (range 6–13), and 18 were with a borderline risk at a median age of 13 days (9–28). None of the borderline risks were IOPD patients. Among the 14 at a high-risk of Pompe disease, four were found to have cardiomyopathy, and six were classified as potential late-onset Pompe disease. The four classic IOPD newborns, three of the four having at least one allele of the cross-reactive immunologic material (CRIM)-positive variant, started enzyme replacement therapy (ERT) at a median age of 9 days (8–14). Western Blot analysis and whole gene sequencing confirmed the CRIM-positive status in all cases. Here, we focus on the patient without the known CRIM-positive variant. Doing ERT before knowing the CRIM status created a dilemma in the decision and was discussed in detail. Our Pompe disease screening and diagnostic program successfully detected and treated patients with IOPD in time. However, the timely exclusion of a CRIM-negative status, which is rare in the Chinese population, is still a challenging task.

Highlights

Pompe disease, a genetic disorder caused by variants of the glucosidase alpha acid (GAA) gene, leads from acid alpha-glucosidase (GAA) deficiency
We have performed newborn screening (NBS) for Pompe disease [1] since 2005, and our results demonstrate that the early initiation of treatment improves the prognosis infantile-onset Pompe disease (IOPD) patients [2], confirming the value of newborn screening for Pompe disease
enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) may trigger an immune response with neutralizing antibodies, especially in patients negative for the cross-reactive immunologic material (CRIM) [7]

Summary

Introduction

A genetic disorder caused by variants of the glucosidase alpha acid (GAA) gene, leads from acid alpha-glucosidase (GAA) deficiency. We have performed newborn screening (NBS) for Pompe disease [1] since 2005, and our results demonstrate that the early initiation of treatment improves the prognosis IOPD patients [2], confirming the value of newborn screening for Pompe disease. The phenotype cannot be predicted by GAA activity [3,4]. Mutation analysis of the GAA gene can predict the phenotype in a portion of patients [5]. ERT with rhGAA may trigger an immune response with neutralizing antibodies, especially in patients negative for the cross-reactive immunologic material (CRIM) [7]. In 2005, we were the first to implement Pompe disease newborn screening [1]. The hospital staff work closely with the screening center in order to make a timely management of IOPD. We describe our practice in the past seven years

Methods

Performance of Screening and Diagnostic Testing

Case Description