• Journal of Korean Neurosurgical Society
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• 제53권3호
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• pp.187-189
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• 2013

We report an unusual case of cerebral aneurysmal subarachnoid hemorrage (SAH) with Fabry's disease. A 42-year-old woman presented with aneurysmal SAH originated from a saccular aneurysm of the right posterior communicating artery. The patient was treated by an endovascular coil embolization of aneurysm. Postoperatively the patient recovered favorably without any neurological deficit. During her admission, the patient had a sign of proteinuria in urine analysis. The pathologic findings of kidney needle biopsy implied nephrosialidosis (mucolipidosis of lysosomal stroage disease), which is consistent with a Fabry's disease. It is uncommon that Fabry's disease is presented with aneurysmal SAH, especially in middle-aged patients, but could be a clinical concern. Further investigations are needed to reveal risk factors, vascular anatomy, and causative mechanisms of Fabry's disease with aneurysmal SAH.

• Childhood Kidney Diseases
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• 제20권2호
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• pp.79-82
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• 2016

Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme ${\alpha}-galactosidase$ A, resulting in the accumulation of glycosphingolipids within the lysosomes of various cell types. It has a wide spectrum of clinical phenotypes, and renal failure is a serious complication. Fabry disease is confirmed either by measurement of ${\alpha}-galactosidase$ A activity or by genetic testing for GLA mutations. Renal biopsy findings on light microscopy, specifically enlarged podocytes with foamy cytoplasm, and osmiophilic inclusion bodies in the cytoplasm in all types of renal cells on electron microscopy, are characteristic of this disease. The predominant differential diagnosis is iatrogenic phospholipidosis in association with certain drugs that can cause cellular injuries indistinguishable from Fabry disease. Here, we report the case of a 10-year-old boy with microscopic hematuria who underwent a renal biopsy that showed morphological findings consistent with Fabry disease, although the patient had neither a GLA mutation nor a history of drug consumption. Six years later, spontaneous regression of this renal pathology was observed in a second renal biopsy examination.

• Mass Spectrometry Letters
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• 제6권4호
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• pp.116-119
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• 2015

Globotriaosylsphingosine (lyso-Gb3) is considered as one of the biological marker for Fabry disease. To date, a reliable biomarker that reflects disease severity and progression has not been discovered to guide the management of Fabry disease. A new method included a simple protein precipitation with acetonitrile in 100 μL of plasma following analyte separation on an Phenomenex Kintex- C18 column using a gradient elution (0.1% formic acid in 5-90% acetonitrile). Total run time was within 12 min including sample preparation and MS/MS analysis. The limit of detection and limit of quantitation were 1 ng/mL and 2 ng/mL, respectively. The calibration curve was linear over the concentration range of 2.0-200.0 ng/mL (r² = 0.9999). Inter-day accuracy and precision at 7 level were 93.4-100.7% with RSD of 0.55-5.97%. Absolute recovery was 97.6-98.6%. The method was applied to human and mice plasma, proved the suitability for quantification of lyso-Gb3 for screening, diagnosis and therapeutic monitoring of Fabry disease patients.

• The Korean Journal of Pain
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• 제23권3호
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• pp.207-210
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• 2010

Fabry disease is an X-linked lysosomal disease caused by deficiency of ${\alpha}$-galactosidase, in which early diagnosis may be missed due to the wide variety of clinical symptoms presenting during disease progression. A 13 year-old boy visited our pain clinic complaining of pricking and burning pain in the toe tips of both feet. Continuous epidural infusion for pain management was performed because of oral analgesics ineffectiveness. The patient underwent ${\alpha}$-galactosidase A (GLA) enzyme analysis based on the clinical impression of Fabry disease from pain with a peripheral neuropathic component and history of anhidrosis. He was diagnosed with Fabry disease after confirming mutation of the GLA gene through a screening test of GLA activity. Enzyme replacement therapy was initiated and pain was tolerated with oral analgesics.

• 약학회지
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• 제60권1호
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• pp.15-20
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• 2016

Globotriaosylsphingosine (lyso Gb3) is considered as one of the biomarkers for Fabry disease. A rapid and simple UPLC-MS/MS method was developed for the determination of reliable biomarker, lyso Gb3. Total analytical procedure takes only 15 min including sample preparation and MS/MS analysis. Limit of detection was 0.85 ng/ml (S/N=3). The calibration curve was linear over the range of 2.0~400.0 ng/ml ($R^2=0.9999$). Inter-day and intra-day assay accuracy were 93.4~100.6% (RSD, 0.6~6.0%) and 97.5~100.7% (RSD, 3.6~5.2%). Absolute recoveries of 97.6~98.6 showed excellence of a new analytical method. The method was applied to human and mice urines, proved the suitability for the quantification of lyso-Gb3 for screening, diagnosis and therapeutic monitoring of Fabry disease patients.

• 대한유전성대사질환학회지
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• 제17권3호
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• pp.92-95
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• 2017

Fabry 병은 성염색체 연관 유전성 리소좀 대사 질환으로 ${\alpha}$-galactosidase A 를 코딩하는 GLA 유전자의 변이로 인한 ${\alpha}$-galactosidase A 효소의 결핍에 의해 발생한다. 이 질환은 globotriaosylceramide (GL-3) 및 관련된 글리코스핑고리피드(glycophospholipids)가 신장 사구체, 심근, 후근 신경절 및 자율 신경계, 혈관 내피 세포 및 평활근 등에 축적되어 사지 말단 동통, 신부전, 심부전 등의 다양한 임상양상을 보이게 된다. 대증적 요법으로만 치료하던 Fabry 병은 효소대체요법의 발전으로 신부전을 포함하여, 심각한 합병증의 예방 및 호전과 함께 질환의 예후를 향상시키고 있다. 또한 사지 말단 동통은 Fabry 병 환자들의 삶의 질을 특히 떨어뜨리며, 적절한 효소대체요법에 효과가 있는 것으로 알려져 있다. 저자들은 40대 후반에 Fabry 병을 진단받고 효소대체요법을 시작하여 사지 말단 동통이 호전된 중국인 남자 환자에 대해 보고하는 바이다.

• 대한유전성대사질환학회지
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• 제14권1호
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• pp.37-41
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• 2014

Fabry disease is an X-linked disease caused by deficiency of the lysosomal enzyme alpha-galactosidase A. Affected males present anhydrosis, acroparesthesia and angiokeratoma, and subsequently cardiac, cerebral and renal complications are followed. Females and atypical variants show heterogeneous clinical symptoms. In 2001, two recombinant enzymes were approved for Fabry disease: agalsidase alpha and agalsidase beta. Since the introduction of enzyme replacement therapy (ERT), the number of long-term follow-up studies has been reported. Long-term ERT showed effectiveness on renal function in patients with chronic kidney disease, decrease or stabilization of left ventricular mass, and improvement of pain and quality of life. However, there were limited effects on cerebrovascular events and their mortality. Current literatures on the clinical effect of ERT have reported limited datain adult patients who have already advanced disease. Therefore, further study for pre-symptomatic patients and atypical variants is needed to verify the impact of ERT. This review summarized recent progresses in ERT and limitations of long-term effect of ERT in patients with Fabry disease.

• Journal of mucopolysaccharidosis and rare diseases
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• 제4권1호
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• pp.21-25
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• 2018

Fabry disease is a hereditary lysosomal storage disorder caused by the reduction or absence of lysosomal enzyme alpha-galactosidase A and the accumulation of glycosphingolipids, such as globotriaosylceramide (Gb3), in various organs, including the heart. The prevention of cardiac involvement in Fabry disease can only be achieved by enzyme replacement therapy (ERT), and the method of assessing the efficacy of ERT should be confirmed. Changes in the electrocardiogram, such as the shortening of PQ interval, prolongation of QTc and repolarization abnormalities as well as left ventricular hypertrophy in voltage criteria, can be used to identify Fabry disease patients; however, the usefulness of electrocardiograms for evaluating the efficacy of ERT is limited. The assessment of left ventricular hypertrophy using echocardiography has been established to evaluate the efficacy of ERT during long-term period. A new technique involving speckled tracking method might be useful for detecting early cardiac dysfunction and identifying the effect of ERT for a relatively short period. The estimation of left ventricular hypertrophy using cardiac magnetic resonance (CMR) is also useful for assessing the efficacy of ERT. Identifying late gadolinium enhancement in CMR may affect the effectiveness of ERT, and the new technique of T1 mapping might be useful for monitoring the accumulation of Gb3 during ERT. Histopathology in cardiac biopsy specimens is another potentially useful method for identifying the accumulation of GB3; however, the use of histopathology to evaluate of the efficacy of ERT is limited because of the invasive nature of an endomyocardial biopsy.

• Clinical and Experimental Pediatrics
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• 제53권2호
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• pp.235-238
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• 2010

파브리병은 알파-갈락토시다아제(alpha galactosidase) A 효소에 위치하는 유전자 변이에 의한 글라이코스핑고리피드(glycospingolipid) 대사이상에 의한 질환으로 X-염색체와 연관된다. 말단 지각이상을 호소하던 12세 남자 환자와 증상이 미미한 그의 형에서 알파-갈락토시다아제 A 효소 활성도 측정과 유전자 변이 확인을 통하여 파브리병을 확진한 2례를 보고하고자 한다.

• 대한유전성대사질환학회지
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• 제15권3호
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• pp.127-137
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• 2015

본 연구에서는 파브리병의 마우스 모델과 세포모델을 대상으로 miRNA expression microarray를 적용시켜 질환 모델과 정상 대조군 간의 전체 miRNA의 발현 차이를 조사하였고, 발현량에서 차이를 보인 특정 miRNA를 선별한 후, 해당 miRNA의 표적 유전자의 발현량 변화를 살펴보아 파브리병의 신장병변에 대한 바이오마커 발굴과 발병기전을 알아보고자 하였다. MicroRNA array 결과, 파브리 마우스 신장 조직의 경우, 1,247개의 분석 대상 miRNA 중 5개가 발현이 증가되어 있으며 3개가 발현이 감소되어 있음을 확인하였다. 그 중에서 miR-149-5p의 발현이 파브리 마우스의 신장에서 2배 이상 감소되어 있으며, 특히 35주령 이하의 파브리 마우스에서 이러한 감소현상이 나타남을 확인하였고, 또한 lyso-Gb3를 처리하여 배양한 SV40 MES 13 세포에서도 miR-149-5p의 발현이 감소됨을 알 수 있었다. miR-149-5p의 발현감소는 EMT와 관련된 유전자의 발현을 증가시킴을 확인하였다. 본 연구를 통해 miR-149-5p의 생체지표로서의 가능성과 함께 miR-149-5p의 발현감소가 EMT를 통한 파브리병에서의 사구체 섬유화에 관여할 것이라는 가능성을 제시하고 있다.