Newborn screening for Pompe disease in Japan

Abstract

Pompe disease is caused by a deficiency of acid alpha-glucosidase (GAA) that results in glycogen accumulation, primarily in muscle. Newborn screening (NBS) for Pompe disease has been initiated in Taiwan and is reportedly successful. However, the comparatively high frequency of pseudodeficiency allele makes NBS for Pompe disease complicated in Taiwan. To investigate the feasibility of NBS for Pompe disease in Japan, we obtained dried blood spots (DBSs) from 496 healthy Japanese controls, 29 Japanese patients with Pompe disease, and five obligate carriers, and assayed GAA activity under the following conditions: (1) total GAA measured at pH 3.8, (2) GAA measured at pH 3.8 in the presence of acarbose, and (3) neutral glucosidase activity (NAG) measured at pH 7.0 without acarbose. The % inhibition and NAG/GAA ratio were calculated. For screening, samples with GAA<8% of the normal mean, % inhibition>60%, and NAG/GAA ratio>30 were considered to be positive. Two false positive cases (0.3%) were found, one was a healthy homozygote of pseudodeficiency allele (c.1726G>A). The low false-positive rate suggests that NBS for Pompe disease is feasible in Japan.