Identification of a novel mutation and prevalence study for fabry disease in Japanese dialysis patients
Tomoya Nishino1, Yoko Obata, Akira Furusu
1Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Insights
Fabry disease affects patients on maintenance dialysis. Screening 933 patients in Nagasaki, Japan, revealed a prevalence of 0.32%, highlighting the need for early detection in hemodialysis populations.
Area of Science:
- Genetics
- Nephrology
- Biochemistry
Background:
- Fabry disease is a genetic lysosomal storage disorder caused by alpha-galactosidase A deficiency.
- It leads to globotriaosylceramide accumulation and multiorgan damage, particularly progressive kidney disease.
- Higher prevalence in hemodialysis patients suggests a link between Fabry disease and end-stage renal disease.
Purpose of the Study:
- To determine the prevalence of Fabry disease among patients undergoing maintenance dialysis in Nagasaki Prefecture, Japan.
- To evaluate the effectiveness of dried blood spot screening for Fabry disease in this population.
- To identify any novel mutations or genetic variations associated with Fabry disease.
Main Methods:
- Screening of 933 maintenance dialysis patients in Nagasaki Prefecture for alpha-galactosidase A activity using dried blood spots.
- Clinical assessment of patients with low enzyme activity.
- Genetic analysis of the alpha-Galactosidase A gene to confirm mutations.
Main Results:
- 55 out of 933 patients (5.9%) exhibited low alpha-galactosidase A activity.
- Three patients (one male, two females) were confirmed to have alpha-Galactosidase A mutations, yielding a prevalence of 0.32%.
- A novel mutation was identified, and the E66Q variant was excluded as a possible polymorphism, leading to a final calculated prevalence of 0.11% in the hemodialysis population.
Conclusions:
- The prevalence of Fabry disease in maintenance dialysis patients in Nagasaki Prefecture is 0.32%.
- Dried blood spot screening is a simple and effective method for identifying Fabry disease in hemodialysis patients.
- Early detection and management are crucial for patients with Fabry disease, especially those with kidney involvement.
Abstract:
Fabry disease--a genetic disorder characterized by the accumulation of globotriaosylceramide in cell lysosomes resulting from an X-linked deficiency of α-galactosidase A activity--presents with multiorgan manifestations, including progressive renal disease. Recently, its prevalence has been reported to be higher in hemodialysis (HD) patients than in the general population. We, therefore, examined patients on maintenance dialysis living in the Nagasaki Prefecture, Japan, to clarify the prevalence of Fabry disease. We screened 933 patients on maintenance dialysis, who were residents of Nagasaki Prefecture in Japan, for α-galactosidase A activity using a dried blood spot on filter paper. Patients with low α-galactosidase A activity were clinically assessed; subsequently, genetic analysis of the α-Galactosidase A gene (MIM:30064) was performed in these patients. Of the 933 patients, 55 had low α-galactosidase A activity; of these, one male and two females had α-Galactosidase A mutations. The prevalence of Fabry disease was thus 0.32%, which was similar to that reported previously. However, one mutation was newly identified, while the E66Q mutation observed in two patients was as previously identified. These two patients with the E66Q mutation were excluded because of the possibility of polymorphism; the prevalence of Fabry disease in the HD population was finally calculated to be 0.11%. The prevalence of Fabry disease in patients on maintenance dialysis living in Nagasaki Prefecture was 0.32%. Dried blood spot screening was considered as a simple and effective method for screening patients on maintenance dialysis for Fabry disease.
Related Concept Videos
01:24Chronic Kidney Disease II: Clinical Manifestations
01:25Drug Dosing in Renal Diseases: Measurement of Glomerular Filtration Rate
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:29Pharmacogenomics: Identification of New Drug Targets
01:25Chronic Kidney Disease I: Introduction
01:25Hemodialysis I: Introduction