Newborn genetic screening for Fabry disease: Insights from a retrospective analysis in Nanjing, China

Area of Science:

• Genetics
• Rare Diseases
• Biochemistry

Background:

• Fabry disease (FD) is an X-linked disorder caused by alpha-galactosidase A deficiency.
• Early diagnosis and intervention are critical for managing FD complications and improving prognosis.
• Current diagnostic methods face challenges, particularly for female and late-onset patients, necessitating improved screening strategies.

Purpose of the Study:

• To evaluate the effectiveness of genetic screening for pathogenic GLA variants in newborns for early Fabry disease detection.
• To determine the incidence and prevalent pathogenic variants of FD in the Nanjing region of China.
• To compare the utility of genetic screening versus enzyme activity testing for identifying at-risk individuals.

Main Methods:

• Retrospective analysis of genetic screening results for pathogenic GLA variants.
• Screening of 17,171 newborns for genetic markers associated with Fabry disease.
• Analysis of variant prevalence and residual enzyme activity.

Main Results:

• An estimated incidence of Fabry disease of approximately 1 in 1321 was found in the Nanjing region.
• The most common pathogenic GLA variant identified was c.640-801G > A (46.15%).
• The pathogenic variant c.911G > C exhibited marginally higher residual enzyme activity, suggesting genetic screening's potential advantage for specific patient groups.

Conclusions:

• GLA genetic screening is a valuable tool for the early diagnosis of Fabry disease in newborns.
• Genetic screening may be more effective than enzyme activity testing for identifying potential female and late-onset Fabry disease patients.
• This study provides a reference for improving early diagnosis, treatment strategies, and genetic counseling for Fabry disease.