Fabry disease screening in high-risk populations in Japan: a nationwide study
Shinichiro Yoshida1,2, Jun Kido3, Takaaki Sawada1
1Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto City, Kumamoto, 860-8556, Japan.
Insights
This study identified 236 Fabry disease (FD) patients through high-risk screening, aiding early diagnosis and treatment selection. The findings highlight the utility of simple screening protocols for detecting FD in at-risk populations.
Area of Science:
- Genetics
- Metabolic Disorders
- Rare Diseases
Background:
- Fabry disease (FD) is an X-linked inherited disorder caused by GLA gene mutations, leading to alpha-galactosidase A (α-Gal A) deficiency.
- Accumulation of metabolites due to α-Gal A deficiency causes multisystemic dysfunction.
- Recent studies indicate an increased incidence of FD, with many patients remaining undiagnosed or misdiagnosed.
Purpose of the Study:
- To identify patients with Fabry disease (FD) through high-risk screening.
- To evaluate the effectiveness of a screening protocol in a large cohort with renal, cardiac, or neurological manifestations.
- To identify GLA variants and assess suitability for migalastat treatment.
Main Methods:
- High-risk screening of 18,135 individuals with renal, cardiac, or neurological manifestations across Japan.
- Analysis of α-Gal A activity and GLA gene sequencing for diagnosis.
- Inclusion of family members with a history of FD.
Main Results:
- 236 patients with FD were identified from 18,199 participants.
- 101 GLA variants, including 26 novel ones, were detected in 143 families.
- 33% of FD patients and 39% of GLA variants were suitable for migalastat treatment.
Conclusions:
- A simple dried blood spot screening protocol can aid in the early diagnosis of FD.
- This screening approach is valuable for identifying high-risk and underdiagnosed patients.
- Early diagnosis facilitates the selection of appropriate treatments, such as migalastat.
Background:
Fabry disease (FD) is a X-linked inherited disorder caused by mutations in the GLA gene, which results in the deficiency of α-galactosidase A (α-Gal A). This leads to the progressive accumulation of metabolites, which can cause multisystemic dysfunction. A recent screening study among neonates reported an increase in the incidence of FD, and numerous FD patients remain undiagnosed or even misdiagnosed. Therefore, this study aimed to identify patients with FD by performing high-risk screening in 18,135 individuals, enrolled from October 2006 to March 2019, with renal, cardiac, or neurological manifestations from all prefectures in Japan. A total of 601 hospitals participated in this study.
Results:
Low α-Gal A activity was detected in 846 individuals, with 224 of them diagnosed with FD by GLA sequencing. Cases with a family history of FD (n = 64) were also subjected to sequencing, without α-Gal A assay, as per individual request, and 12 of them were diagnosed with a variant of FD. A total of 236 patients with FD (97 males and 139 females) were identified from among 18,199 participants. A total of 101 GLA variants, including 26 novel variants, were detected in the 236 patients with FD from 143 families, with 39 amenable variants (39%) and 79 of the 236 patients (33%) suitable for migalastat treatment.
Conclusions:
From among 18,199 participants, 101 GLA variants, including 26 novel variants, were identified in the 236 patients with FD from 143 families. Migalastat was identified as a suitable treatment option in 33% of the patients with FD and 39% of the GLA variants were detected as amenable. Therefore, the simple screening protocol using dried blood spots that was performed in this study could be useful for early diagnosis and selection of appropriate treatments for FD in high-risk and underdiagnosed patients with various renal, cardiac, or neurological manifestations.
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