• 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.

• 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.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.11 no.1
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• pp.27-32
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• 2011

최근 유전공학의 발달로 리소좀 축적 질환에서 효소 치료제가 개발되어 실제 치료에 사용되고 있다. 현재 효소 보충 치료가 가능한 리소좀 축적 질환에는 고셔병(Gaucher disease), 파브리병(Fabry disease), 폼페병(Pompe disease), 뮤코다당체침착병(Mucopolysaccharidosis, MPS) 1형, 2형, 6형이 있으며 비교적 안전하면서 증상 완화에도 효과적으로 보인다. 그러나 이미 진행이 된 증상에 대해서는 비가역적이므로 조기에 진단을 하여 치료를 시작하는 것이 중요하다. 효소 보충 치료의 장기간에 걸친 치료 효과에 대해서 지속적인 평가가 필요하며 무엇보다 뼈와 중추신경계에 대한 효과는 제한적이므로 이에 대한 새로운 치료법의 개발이 필요하다.

• Journal of Genetic Medicine
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• v.15 no.1
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• pp.28-33
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• 2018

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficiency of ${\alpha}$-galactosidase A. Patients with classical FD present acroparesthesia, hypohidrosis, cornea verticillata, disseminated angiokeratoma, and microalbuminuria in childhood, and develop life-threatening renal, cardiac, and cerebrovascular complications typically after the fourth decade of life. To date, more than 700 mutations responsible for FD have been identified in the human GLA gene. Herein, we report a novel GLA mutation, c.1117_1141del25 (p.Gly373Profs*10), identified in an 11-year-old Korean boy with FD presenting early cardiac and neurologic manifestation and in other affected family members. The boy had acroparesthesia, hypohidrosis, cornea verticillata, and left ventricular hypertrophy. His mother and sister also had acroparesthesia. Two males on the mother's side had similar pain and died of unknown causes. The plasma ${\alpha}$-galactosidase A activity (4.1 nmol/hr/mg protein) of the patient was markedly lower than the mean value of the controls. The plasma level of globotriaosylsphingosine was elevated in the patient and all the carriers. We concluded the novel GLA mutation c.1117_1141del25 is a pathogenic mutation for FD, probably related to the early cardiac manifestation of FD.