• Clinical and Experimental Pediatrics
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• 제55권2호
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• pp.48-53
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• 2012

Purpose: Gaucher disease is caused by a ${\beta}$-glucocerebrosidase (GBA) deficiency. The aim of this study is to investigate the clinical and genetic characteristics according to subtypes of Gaucher disease in the Korean population. Methods: Clinical findings at diagnosis, $GBA$ mutations, and clinical courses were reviewed in 20 patients diagnosed with Gaucher disease. Results: Eleven patients were diagnosed with non-neuronopathic type, 2 with acute neuronopathic type, and 7 with chronic neuronopathic type. Most patients presented with hepatosplenomegaly, thrombocytopenia, and short stature. In the neuronopathic group, variable neurological features, such as seizure, tremor, gaze palsy, and hypotonia, were noted at age $8.7{\pm}4.3$ years. B cell lymphoma, protein-losing enteropathy, and hydrops fetalis were the atypical manifestations. Biomarkers, including chitotriosidase, acid phosphatase, and angiotensin-converting enzyme, increased at the initial evaluation and subsequently decreased with enzyme replacement treatment (ERT). The clinical findings, including hepatosplenomegaly, thrombocytopenia, and skeletal findings, improved following ERT, except for the neurological manifestations. L444P was the most common mutation in our cohort. One novel mutation, R277C, was found. Conclusion: Although the clinical outcome for Gaucher disease improved remarkably following ERT, the outcome differed according to subtype. Considering the high proportion of the neuronopathic form in the Korean population, new therapeutic strategies targeting the central nervous system are needed, with the development of a new scoring system and biomarkers representing clinical courses in a more comprehensive manner.

• 대한유전성대사질환학회지
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• 제6권1호
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• pp.58-62
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• 2006

Gaucher disease is an inherited disorder due to a deficiency in the activity of glucocerebrosidase (EC. 3.2.1.45) by genetic mutation which resulted from missense, nonsense, frameshift, deletion in long arm 21 of chromosome 1 (1q21). Gaucher disease is classified into the main three types as type 1 (nonneuronopathic), type 2 (acute neuronopathic) and type 3 (subacute neuronopathic) according to the progressive phase of manifestations and nervous system involvement. Gaucher disease patients had been treated by using the method as splenectomy and bone marrow transplantation. But enzyme replacement therapy as a more effective treatment has been available since the early 1990's. In order to treat Gaucher disease efficiently by using ERT, it is necessary to chase the progress of the therapy. In this study, therefore, we tried to chase the progress of the ERT by using the measurement of chitotriosidase activity in Gaucher disease patients.

• Journal of mucopolysaccharidosis and rare diseases
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• 제5권1호
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• pp.1-7
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• 2021

Gaucher disease (GD, OMIM #230800 OMIM#230800) is a rare, autosomal recessive inherited metabolic disorder caused by mutation in GBA1 encoding the lysosomal enzyme, glucocerebrosidase. The deficiency of glucocerebrosidase leads to an accumulation of its substrate, glucosylceramide in macrophages of various tissues. Common clinical manifestations include cytopenia, splenomegaly, hepatomegaly, and bone lesions. The phenotype of GD is classified into three clinical categories: Type 1 (non-neuronopathic) is characterized by involvements on the viscera, whereas types 2 and 3 (neuronopathic) are associated with not only visceral symptoms but also neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 should be identified as they may be of prognostic value in some cases. Biomarkers including Chitotriosidase, CCL18, and glucosylsphingosine (lyso-GL1) are useful in diagnosis and treatment monitoring. Currently available disease-specific treatment in Korea consists of intravenous enzyme replacement therapy and substrate reduction therapy. For enhancing long-term prognosis, the onset of Parkinson's disease and Lewy body dementia, or the occurrence of a blood disease or cancer (hepatocellular carcinoma) should be monitored in older patients. The development of new strategies that can modify the neurological phenotype are expected, especially in Asia including Korea, where the prevalence of neuronopathic GD is relatively higher than that in western countries.

• 대한유전성대사질환학회지
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• 제20권1호
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• pp.1-13
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• 2020

Gaucher disease (GD)는 glucocerebrosidase 유전자(GBA)의 돌연변이에 의하여 발병하는 전세계적으로 가장 유병율이 높은 리소좀 축적질환이다. GD는 신경학적인 증상의 유무에 따라 3가지 임상형으로 구분된다. 신경병증 GD인 2형과 3형의 경우는 대뇌에서 glucosylceramide (GlcCer)와 glucosylsphingosine (GlcSph)의 농도가 증가하면서 신경세포의 심각한 손실이 야기되는 특징을 보인다. 신경교종에서 유래한 H4 세포를 GD에서 증가하는 기질인 GluCer와 GlcSph를 첨가하여 배양하였을 때, 심각한 DNA손상과 더불어 세포의 사멸이 야기되는 것과 이러한 신경세포의 사멸은 GluCer 보다는 GlcSph을 처리하였을 때 더 현저하게 증가하는 것을 관찰하였다. H4 세포에 히스톤 탈아세틸화 효소(HDAC) 6의 저해제인 tubacin과 GlcSph을 함께 처리하였을 경우에는 DNA손상은 물론 GlcSph에 의하여 유도된 세포사멸과 관련된 단백질 인자들의 발현이 모두 감소되었다. 본 연구를 통해 GlcSph이 세포사멸을 통하여 신경병증 GD의 발병에 주요한 역할을 한다는 것을 알 수 있었고, HDAC6 저해제가 신경병증 GD 환자를 위한 치료제 후보물질로 제시될 수 있는 가능성을 확인하였다.

• Molecules and Cells
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• 제38권9호
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• pp.806-813
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• 2015

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrowderived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

• 대한유전성대사질환학회지
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• 제17권2호
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• pp.63-68
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• 2017

고셔병은 리소좀축적병으로 lysosomal hydrolase glucocerebrosidase 결여로 간비장비대, 골격계 증상, 빈혈, 혈소판 감소증의 증상을 나타내는 드문 상염색체 유전 질환이다. 본 증례에서는 2세 여아에서 간비장비대, 다리 통증, 성장부진이 관찰되어 시행한 단순 방사선 촬영 검사에 Erlenmeyer flask 변형을 확인하여 고셔병을 의심하였고 효소 분석 및 유전자 검사를 통해 확진하였다. 환아에서 한국인 비신경형 고셔병에서만 관찰되는 G46E 돌연변이를 확인하였고 1년 간의 효소 대체 요법을 통해 성장, 혈액학적 지표, 간비장비대 및 골증상의 호전을 확인하였기에 본 증례를 보고하는 바이다.

• 대한유전성대사질환학회지
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• 제17권2호
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• pp.55-62
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• 2017

고셔병은 리소좀축적병으로 lysosomal hydrolase glucocerebrosidase 결여로 간비장비대, 골격계 증상, 빈혈, 혈소판 감소증의 증상을 나타내는 드문 상염색체 유전 질환이다. 본 증례에서는 18개월 남아에서 간비장비대, 성장 부진이 관찰되었으며 안구 운동 장애 및 발달 지연이 동반되어 제 3형 고셔병을 의심하였고 효소 분석 및 유전자 검사를 통해 확진하였다. 환아에서 한국인 신경형 고셔병에서 흔하게 관찰되는 c.754T>A(F213I)와 c.887G>A (R257Q)가 이형 접합체 돌연변이로 확인되었고 17개월 간의 효소 대체 요법을 통해 성장, 혈액학적 지표, 간비장비대 및 골증상은 호전되었지만 신경학적 증상의 호전은 없었고, 샤프론 중암브록솔에 유의한 반응이 있다고 알려져 있는 c.754T>A이 확인됨에 따라 환아에서 3개월간 암브록솔 치료를 시도하였지만 뚜렷한 임상적 치료 효과를 확인할 수 없었기에 본 증례를 보고하는 바이다.