Newborn screening for Pompe disease in Japan

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Pompe disease results from acid alpha-glucosidase (GAA) deficiency, leading to glycogen buildup in muscles.
• Newborn screening (NBS) for Pompe disease is successful in Taiwan but complicated by pseudodeficiency alleles.
• Investigating NBS feasibility in Japan is crucial due to potential genetic variations.

Purpose of the Study:

• To evaluate the feasibility of newborn screening for Pompe disease in Japan.
• To assess the effectiveness of specific enzyme activity assays in identifying Pompe disease.
• To determine the prevalence and impact of pseudodeficiency alleles on NBS in the Japanese population.

Main Methods:

• Dried blood spots from 496 healthy Japanese controls, 29 Pompe disease patients, and 5 carriers were analyzed.
• Acid alpha-glucosidase (GAA) activity was measured at pH 3.8 (total and with acarbose inhibition).
• Neutral glucosidase activity (NAG) was measured at pH 7.0; % inhibition and NAG/GAA ratio were calculated for screening.

Main Results:

• A screening strategy using GAA activity, % inhibition, and NAG/GAA ratio identified potential cases.
• Two false positive cases (0.3%) were detected, including one with a pseudodeficiency allele homozygote (c.1726G>A).
• The low false-positive rate indicates the reliability of the proposed screening method.

Conclusions:

• Newborn screening for Pompe disease is feasible in Japan using the developed assay methods.
• The assay effectively distinguishes between true Pompe disease cases and carriers of pseudodeficiency alleles.
• This study supports the implementation of NBS for Pompe disease in Japan.