Background: Our team has implemented a newborn screening program for fabry disease in Taiwan since 2008. However, current enzyme-based newborn screening method is not reliable to detect heterozygous female patients. Estimatedly, more than 80% of female patients are missed by this enzyme-based screening method. The study aims to develop a simple, fast, reliable, and cost-effective method to screen fabry disease in females.
Methods: Because the GLA mutations are limited to only 21 different pathogenic mutations according to the reports from 668,087 newborns via our newborn screening program, a customized mass screening method for fabry mutations by Agena iPLEX assay is established in Taiwan. Simultaneously, 21 mutations can be analyzed in one reaction for one person.
Results: There were 20,154 female infants participated in this program. A total of 54 IVS4+919G>A and one c.656T>C female infants were identified. The incidence of female infants with fabry mutations is as high as 1/366. Owing to the particularity of 21 mutations detected in a single multiplex reaction, the cost of this method can be less than US $10 per infant in the Fabry mutation screening.
Conclusions: In this study, we demonstrated that the Agena iPLEX assay is a powerful tool with high specificity and sensitivity for germline mutation screening. The detectivity of fabry disease in females can be elevated by this DNA mass-based genotyping method. Considering the low cost, rapidity and flexibility of the Agena iPLEX assay, it has a great potential to be incorporated into the newborn screening in Taiwan.
