• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.3
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• pp.127-137
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• 2015

Purpose: The main aim of this study was to compare and analyze expression profiles of microRNAs (miRNAs) to establish miRNA signature of Fabry nephropathy related epithelial mesenchymal transition (EMT). Methods: Expression profiles of miRNAs in kidney tissue samples and cell lines from normal and Fabry disease mouse model were examined by miRNA expression microarray analysis followed by quantitative real-time polymerase chain reaction analysis (qRT-PCR). Results: In the miRNA expression microarray analysis of Fabry mouse kidney tissues compared to wild type mouse, 5 and 3 miRNAs among 1,247 miRNAs examined were up- and down-regulated, respectively. Among them, miR-149-5p was down-regulated about 2-fold in Fabry kidney samples. The down-regulations of miR-149-5p were observed in kidney tissues of under 35 week-old-Fabry mice. However, this down-regulation was not observed in kidney tissues of 42 week-old Fabry mice. In SV40 MES 13 cells, mouse mesangial cells, treated with globotriaosylsphingosine (lyso-Gb3), miR-149-5p was also downregulated. The down-regulation of miR-149-5p induced up-regulation of its target genes related to EMT. Conclusion: The miRNA expression array and qRT-PCR results show that miR-149-5p expression was decreased in kidney tissues of Fabry mice compared to wild type mice under 35 weeks of age. Along with the observation of miR-149-5p expression in Fabry disease cell models, these results indicate that the down-regulated miR-149-5p were related to the biological response of mesangial cells to lyso-Gb3 and also have influence to the transcriptional up-regulation of its target genes. These results suggest miR-149-5p might play important roles in the Fabry nephropathy.

• Journal of Yeungnam Medical Science
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• v.35 no.2
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• pp.232-235
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• 2018

Fabry disease (FD) is an X-linked, recessively inherited, rare, progressive, disorder of glycosphingolipid metabolism affecting multiple organs resulting in organ dysfunction. It is rare to find only one FD affected subject with a de novo mutation. Here we report a case of a 41-year-old Asian male diagnosed with de novo FD. Comprehensive ophthalmological evaluation was performed using slit lamp, color fundus photography, optical coherence tomography, fluorescein angiography, and indocyanine green angiography. On slit lamp examination, cornea verticillata and slightly tortuous, and aneurysmal dilatation of inferior bulbar conjunctival vessels were observed. Other imaging modalities showed unremarkable findings. Cornea verticillata and inferior bulbar conjunctival vascular abnormalities may be detected earlier than other ocular abnormalities in de novo FDs like hereditary FDs.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.3 no.1
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• pp.62-62
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• 2003

• YAKHAK HOEJI
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• v.51 no.2
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• pp.96-102
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• 2007

Measurement of globotriaosylceramide (Gb3, ceramide trihexoside) in urine has clinical importance for monitoring after enzyme replacement therapy in Fabry disease patients. The disease is an X-linked lipid storage disorder that results from a deficiency of the enzyme ${\alpha}$-galactosidase A (${\alpha}$-Gal A). The lack of ${\alpha}$-Gal A causes an intracellular accumulation of glycosphingolipids, mainly Gb3. A simple, rapid, and highly sensitive analytical method for Gb3 in urine was developed without labor-extensive pre-treatment by electrospray ionization MS/MS (ESI-MS/MS). Only simple 5-fold dilution of urine is necessary for the extraction and isolation of Gb3 in urine. Gb3 in diluted urine was dissolved in dioxane containing C17:0 Gb3 as an internal standard. After centrifugation it was directly injected and analyzed through guard column by in combination with multiple reaction monitoring mode of ESI-MS/MS. Eight isoforms of Gb3 were completely resolved from urine matrix. C24:0 Gb3 occupied 50% of total Gb3 as a major component in urine. Linear relationship for Gb3 isoforms was found in the range of 0.005${\sim}$5.0 ${\mu}$g/ml. The limit of detection (S/N=5) was 0.005 ${\mu}$g/ml and limit of quantification was 0.05 ${\mu}$g/ml for C24:0 Gb3 with acceptable precision and accuracy. Correlation coefficient of calibration curves for 8 Gb3 isoforms ranged from 0.9598 to 0.9975. This method could be useful for rapid and sensitive 1st line Fabry disease screening, monitoring and/or diagnostic tool for Fabry disease.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.68-71
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• 2002

• YAKHAK HOEJI
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• v.55 no.1
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• pp.56-63
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• 2011

Fabry disease (FD) is an X-linked inborn error of glycoshpingolipid metabolism resulting from mutation in the enzyme ${\alpha}$-galactosidase A gene. The disease is an X-linked lipid storage disorder and the lack of ${\alpha}$-Gal A causes an intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb-3). Measurement of Gb-3 in plasma has clinical importance for monitoring after enzyme replacement therapy for confirmed FD patients. Using electrospray ionization MS/MS we had developed, a simple, rapid, and highly sensitive analytical method for Gb-3 in plasma was used for the purpose of screening FD among high risk groups in Korean population. To date, no comprehensive results for FD screening have been performed and reported in Korea. We screened 1,100 outpatients from 13 hospitals (including clinics) to assess the incidence of FD among patients in high risk groups. For patients with borderline level amount of Gb-3, we repeated Gb-3 or performing complementary or confirmative assay with ${\alpha}$-Gal A activity and DNA mutaion analysis for confirmation diagnosis. Of 1,100 we diagnosed 3 FD with 2 classical type and 1 carrier (0.27%).

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.2
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• pp.65-74
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• 2012

• Journal of the Korean neurological association
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• v.36 no.4
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• pp.341-344
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• 2018

It is uncommon for Fabry's disease (FD) patient to present with an isolated ischemic stroke without other typical symptoms or signs of FD. A 48-year-old woman presented with recurrent limb weakness and her brain magnetic resonance imaging revealed multiple ischemic brain lesions. Ten years ago, the patient had been diagnosed with heterozygote FD by the genetic test, but she had not shown any typical symptoms or sign of FD so far. Isolated organ involvement could occur in heterozygote FD.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.24 no.1
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• pp.17-25
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• 2024

Fabry disease (FD) is an X-linked lysosomal storage disorder. It is caused by mutations in the α-galactosidase A gene, which results in deficient or absent activity of α-galactosidase A (α-Gal A). This leads to a progressive accumulation of globotriaosylceramide (Gb3) in various tissues. Manifestations of Fabry disease include serious and progressive impairment of renal and cardiac function. In addition, patients experience pain, gastrointestinal disturbance, transient ischaemic attacks, and strokes. Additional effects on the skin, eyes, ears, lungs, and bones are often seen. Reduced life expectancy and deadly consequences are being caused by cardiac involvement. Chaperone therapy or enzyme replacement therapy (ERT) are two disease-specific treatments for FD. Thus, early detection of FD is critical for decreasing morbidity and mortality. Globotriaosysphingosine (lyso-Gb3) for identifying atypical FD variants and highly sensitive troponin T (hsTNT) for detecting cardiac involvement are both significant diagnostic indicators. This review aimed to offer a basic resource for the early diagnosis and update on the diagnosis of having FD. We will also provide a general diagnostic algorithm and information on ERT and its accompanying treatments.

• BMB Reports
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• v.46 no.3
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• pp.157-162
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• 2013

Human ${\alpha}$-galactosidase A (GLA) has been used in enzyme replacement therapy for patients with Fabry disease. We expressed recombinant GLA from Chinese hamster ovary cells with very high productivity. When compared to an approved GLA (agalsidase beta), its size and charge were found to be smaller and more neutral. These differences resulted from the lack of terminal sialic acids playing essential roles in the serum half-life and proper tissue targeting. Because a simple sialylation reaction was not enough to increase the sialic acid content, a combined reaction using galactosyltransferase, sialyltransferase, and their sugar substrates at the same time was developed and optimized to reduce the incubation time. The product generated by this reaction had nearly the same size, isoelectric points, and sialic acid content as agalsidase beta. Furthermore, it had better in vivo efficacy to degrade the accumulated globotriaosylceramide in target organs of Fabry mice compared to an unmodified version.