To investigate the feasibility of newborn screening for glycogen storage disease type II (GSDII; Pompe disease or acid maltase deficiency) in the Japanese population, we assayed the acid α-glucosidase activity in dried blood spots from 715 Japanese newborns and 18 previously diagnosed patients using a fluorometric procedure. The enzyme activity of apparently healthy newborns showed a bimodal distribution. The median activity of the minor group (31 individuals, 4.3% of the samples) was 6.5 times lower than that of the major group. Four of the 715 control samples (0.56%) fell in the patient range. We then analyzed genomic DNA, extracted from the same blood spots, for the occurrence of two sequence variants, c.1726G>A and c.2065G>A, known to cause "pseudodeficiency". This analysis revealed that 27 of 28 individuals homozygous for c.[1726A; 2065A] belonged to the minor group. One c.[1726A; 2065A] homozygote had just slightly higher activity. Twelve of the 18 patients with GSDII either had one (9 cases) or two (3 cases) c.[1726A; 2065A] alleles. The frequency of this allele was double in the patient compared to the control group (0.42 vs 0.19) at the expense of a lower frequency of the c.[1726G; 2065G] and c.[1726G; 2065A] alleles (0.58 vs 0.71 and 0 vs 0.1). These findings illustrate that c.[1726A; 2065A] homozygosity among apparently healthy individuals (3.9 per 100) complicates newborn screening for GSDII in Japan, and further that one or more pathogenic mutations are associated with the c.[1726A; 2065A] allele.

Additional Metadata
Keywords Acid maltase, Acid α-glucosidase, Dried blood spot, Genetic polymorphism, Glycogen storage disease type II, Newborn screening, Pompe disease
Persistent URL,
Journal Molecular Genetics and Metabolism
Kumamoto, S, Katafuchi, T, Nakamura, K, Endo, F, Oda, E, Okuyama, T, … Okumiya, T. (2009). High frequency of acid α-glucosidase pseudodeficiency complicates newborn screening for glycogen storage disease type II in the Japanese population. Molecular Genetics and Metabolism, 97(3), 190–195. doi:10.1016/j.ymgme.2009.03.004