Newborn screening for Fabry disease in Japan: prevalence and genotypes of Fabry disease in a pilot study
Takahito Inoue1, Kiyoko Hattori, Kenji Ihara
1Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan.
Insights
Newborn screening for Fabry disease (FD) in Japan found a higher prevalence of affected infants than expected. Early detection through mass screening is feasible, but standardized management protocols are needed.
Area of Science:
- Genetics
- Biochemistry
- Pediatrics
Background:
- Fabry disease (FD) is an X-linked lysosomal storage disorder.
- It results from deficient alpha-galactosidase A (GLA) enzyme activity.
- Enzyme replacement therapy (ERT) is available, and newborn screening is being implemented.
Purpose of the Study:
- To conduct a pilot study of newborn mass screening for Fabry disease in Japan.
- To assess the feasibility and initial findings of newborn screening for FD.
Main Methods:
- Measured GLA activity in dried blood spots of neonates using a fluorescence assay.
- Confirmed low GLA activity by measuring GLA activity in white blood cells (WBCs).
- Performed genetic testing to identify GLA gene mutations.
Main Results:
- Screened 21,170 neonates, identifying seven infants (five boys, two girls) with low GLA activity.
- The fluorescence assay proved suitable for newborn mass screening.
- Identified pathogenic mutations (V199M, IVS4+919G>A) and functional mutations (E66Q, c.-10C>T: g.1170C>T).
- Prevalence of test-positive newborns was 1/3024; prevalence of pathogenic mutations was 1/7057.
Conclusions:
- Newborn mass screening for Fabry disease in Japan is feasible.
- The prevalence of FD in newborns may be higher than previously anticipated.
- Standardized management strategies, including ERT, for screen-detected FD cases require development.
Abstract:
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A (GLA) activity. Enzyme replacement therapy (ERT) for FD is available, and newborn mass screening for FD is being implemented. Here, we undertook a pilot study of newborn mass screening for FD in Japan. GLA activity in dried blood spots was measured using a fluorescence assay and confirmed by measurement of GLA activity in white blood cells (WBCs) in infants with abnormally low GLA activity. This was followed up by genetic testing. A total of 21 170 neonates were enrolled in the study. Of these, seven (five boys, two girls) had low GLA activities, which were verified by the WBC GLA activity assay. Thus, the initial fluorescence assay was suitable for newborn mass screening for FD. Pathogenic mutations of the GLA gene, that is, V199M and IVS4+919G>A, were found in two boys and one boy, respectively. Functional mutations, E66Q and c.-10C>T: g.1170C>T, were found in two boys and one girl, respectively. The prevalence of test-positive newborns was 1/3024, while that of those with a pathogenic mutation was 1/7057. The numbers are higher than those previously anticipated. Standardized management for FD found during newborn mass screening, including an ERT regimen, remains to be established.
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