Current status of newborn screening for Pompe disease in Japan

Abstract

Background Pompe disease is an autosomal recessive inherited metabolic disorder caused by a deficiency of the acid α-glucosidase (GAA). Pompe disease manifests as an accumulation of lysosomal glycogen in the skeletal and heart muscle. We conducted newborn screening (NBS) for Pompe disease in Japan from April 2013 to October 2020 to determine the feasibility and utility of NBS for Pompe disease. Results From the 296,759 newborns whose enzyme activity was measured, 107 of which underwent GAA analysis, we found one patient with infantile-onset Pompe disease (IOPD) and seven with potential late-onset Pompe disease (LOPD). We identified 34 pseudodeficient individuals and 65 carriers or potential carriers. The frequency of patients with IOPD was similar to that in the United States, but significantly lower than that in Taiwan. One patient with IOPD underwent early enzyme replacement therapy within a month after birth before presenting exacerbated manifestations, whereas those with potential LOPD showed no manifestations during the follow-up period of six years. Conclusions The frequency of IOPD in Japan was similar to that in the United States, where NBS for Pompe disease is recommended. This indicates that NBS for Pompe disease may also be useful in Japan. Therefore, it should be used over a wider region in Japan.

Newborn screening for Pompe disease in Italy: Long-term results and future challenges

“…About 1 million newborns were screened between 2005 and 2018 (using tandem mass spectrometry (MS/MS) since 2010), and a higher-than-expected PD incidence was found (1:18,090) [ 22 ]. Similar data were obtained by the Japanese NBS program that started in 2013 [ 25 , 26 ].…”

“…- a high number of false positives, especially due to known pseudodeficiency or predicted nonpathogenic variants (15/39 newborns), which impact families and the health care system. This is a common limitation in PD NBS programs, and in most of them pseudodeficiency is detected more often than true deficiency, especially in Asian populations [ 26 , 54 , [86] , [87] , [88] , [89] ], but also in USA (e.g., in Illinois [ 52 ]). Proposals to reduce false positive rates have included biochemical assays (neutral α-glucosidase NAG/GAA ratio and percentage of acarbose inhibition by fluorometry [ 24 , 54 , 90 ]; creatine/creatinine over GAA ratio by MS/MS [ 45 ]), molecular second-tier tests [ 30 , 53 , 91 ], and postanalytical tools (e.g.…”

Muscle biochemical and pathological diagnosis in Pompe disease

“…No patients were pathologically diagnosed by 2020. Meanwhile, newborn screening of Japanese patients via DBS between 2013 and 2020 detected infantile and potential juvenile forms in one and seven, respectively 13. Therefore, recent patients with Pompe disease have been diagnosed without muscle biopsy, which may be due to increased awareness among clinicians, the official approval of ERT for Pompe disease in Japan in 2007, and the introduction of screening for selected high-risk patients via DBS in 2011 and for newborn babies in 2013 7.…”

The Clinical Management of Pompe Disease: A Pediatric Perspective

“…In addition, 34 pseudodeficient individuals and 65 carriers or potential carriers were found. Importantly, the IOPD patients identified were prescribed early ERT before presenting exacerbated manifestations [ 37 ].…”