• The Korean Nurse
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• v.37 no.4
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• pp.38-49
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• 1998

• Journal of Genetic Medicine
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• v.13 no.2
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• pp.72-77
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• 2016

Purpose: Gaucher disease (GD) is the most common lysosomal storage disease caused by beta-glucocerebrosidase (GBA) deficiency. Oral substrate reduction therapy with miglustat ($Zavesca^{(R)}$) was approved for the treatment of adults with GD type 1, for whom enzyme replacement therapy (ERT) is unsuitable or not a therapeutic option. In this study, we report the effect of miglustat ($Zavesca^{(R)}$) in three Korean GD patients. Materials and Methods: Clinical findings comprising age at diagnosis, presenting signs, laboratory findings at diagnosis, GBA activity and mutations, and clinical courses of the three patients were reviewed. Results: Miglustat was administered to three patients who reported allergic reactions during intravenous imiglucerase infusions. One patient withdrew after 15 months of miglustat administration owing to continuous elevation of disease biomarker levels (chitotriosidase, acid phosphatase, and angiotensin-converting enzyme). Poor adherence to medication was suspected but was denied by the patient. In the other two patients, platelet count and levels of hemoglobin and other biomarkers remained stable during miglustat administration. However, they suffered from severe diarrhea and weight loss, which led to miglustat discontinuation after 1 and 12 months of administration. Conclusion: Our study shows that although miglustat is suggested to GD patients as an alternative treatment to ERT, significant adverse reactions may lead to discontinuation of miglustat. In addition, it is difficult to monitor the drug adherence.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.3
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• pp.117-122
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• 2016

제1형 고셔병(Gaucher disease type 1)은 리소좀 효소인 산성 ${\beta}$-글루코시다아제(acid ${\beta}-glucosidase$)의 결핍으로 인한 리소솜 축적 질환이다. 효소 활성도가 감소되어 기질이 축적되어, 간비종대, 빈혈, 혈소판감소증 및 골질환을 포함한 전신 증상이 발생한다. 재조합 효소 단백을 정맥 주입하는 효소 대체요법(Enzyme replacement therapy)는 지난 20년 넘게 고셔병의 표준 치료법이었다. 그러나 성공적인 효소 대체요법에도 불구하고, 심각한 폐증상과 골격 증상 등 고셔병 치료에 여전히 해결되지 않는 문제들이 남아 있다. 기질 감소 치료(Substrate reduction therapy)는 기질의 생합성을 억제하여 축적을 감소시킨다. 최근 새로운 경구용 기질감소 치료제인 엘리글루스타트(eliglustat)가 적합한 CYP2D6 대사 표현형을 가진 고셔병 성인 환자를 위한 1차 치료제로 미국과 유럽에서 승인되었다. 엘리글루스타트가 아직 한국에서는 쓰이지 않고 있지만, 본 종설에서는 문헌 검토를 통해 고셔병의 새로운 치료로서의 효소 대체요법을 소개하고자 한다. 아직 확고한 결론을 도출하기에는 연구 결과가 제한적이기는 하지만, 현재까지의 데이터에 따르면 엘리글루스타트는 임상 효능에 있어서 효소 보충 요법에 비열등성을 보인다. 장기 결과에 대한 추가 연구가 필요하지만, 엘리글루스타트의 승인은 해당 1형 고셔병 성인 환자들에게 경구 치료제라는 새로운 선택을 가능하게 하였다. 향후 국내에서 엘리글루스타트가 처방 가능해 지면, 각 환자 마다 철저한 평가를 통해 치료법을 선택할 수 있도록 해야 할 것이다. 나아가, 국내 1형 고셔병 환자들을 위해 엘리글루스타트의 사용에 관한 임상적 지침 또한 조만간 개발될 필요가 있다.

• Journal of Genetic Medicine
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• v.13 no.2
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• pp.59-64
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• 2016

Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficiency of acid ${\beta}$-glucosidase. The diminished enzyme activity leads to the accumulation of substrates and results in multi-systemic manifestations including hepatosplenomegaly, anemia, thrombocytopenia, and bone diseases. Enzyme replacement therapy (ERT) by infusion of recombinant protein has been the standard treatment for over 20 years. Despite the successful long-term treatment with ERT, several unmet needs remain in the treatment of GD1 such as severe pulmonary and skeletal manifestations. Substrate reduction therapy (SRT) reduces the accumulation of substrates by inhibiting their biosynthesis. Eliglustat, a new oral SRT, was approved in United States and Europe as a first-line therapy for treating adult patients with GD1 who have compatible CYP2D6 metabolism phenotypes. Although eliglustat is not yet available in Korea, introduction and summary of this new treatment modality are provided in this paper by review of literatures. Despite the fact that there are only limited studies to draw resolute conclusions, the current data demonstrated that eliglustat is not inferior to ERT in terms of its clinical efficacy. The approval of eligustat enables eligible adult GD1 patients to have the option of oral therapy although it still needs further studies on long-term outcomes. The individual patient should be assessed carefully for the choice of treatment modality when eliglustat becomes available in Korea. Furthermore, the clinical guidelines for Korean patients with GD1 regarding the use of eliglustat needs to be developed in near future.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.193-200
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• 2019

Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z $588.6{\rightarrow}264.4$ for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625-160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.

• Journal of Genetic Medicine
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• v.17 no.2
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• pp.62-67
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• 2020

Purpose: Eliglustat is an oral substrate reduction therapy (SRT) approved for adults with Gaucher disease type I (GD1) who are extensive, intermediate, or poor CYP2D6 metabolizers. Here we report one-year experience of eliglustat switch therapy from long-term enzyme replacement therapy (ERT) in three adult patients with GD1. Materials and Methods: Medical history, clinical (hemoglobin concentration, platelet count, and bone mineral density) and biochemical parameters (angiotensin converting enzyme, total acid phosphatase, and lyso-gb1) of the patients were collected and evaluated by retrospective review of medical records at every 3, 6, or 12 month after switch to SRT. Results: Patient 1 was a 43-year old female diagnosed GD1 and her clinical and biochemical parameters were stabilized for more than 20 years by ERT. Due to the burden of regular hospital visit, she switched to SRT. During one-year of SRT, clinical parameters and biomarkers were maintained stable. However, after suffering acute febrile illness during SRT, she decided to re-switch to ERT due to concerns about drug interaction. Patient 2 was 41-year old male, younger brother of patient 1 and Patient 3 was 31-year old male. They switched to SRT in clinically stable condition with long-term ERT. The one-year SRT was tolerable without specific safety issue and the clinical parameters were maintained stable. Conclusion: One-year eliglustat therapy in three adult patients with GDI was generally tolerable and effective for maintaining the clinical parameters and biomarkers. However, the drug compliance, concurrent drug interactions, and long-term safety of eliglustat should be carefully monitored.

• 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 Korean Neurosurgical Society
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• v.40 no.2
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• pp.114-116
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• 2006

A Solitary plasmacytoma of bone[SPB] is a rare disease. This paper reports a case of SPB with massive aggregation of histiocytes known as pseudo-Gaucher cells. A 40-year-old male presented with progressive paraparesis and paraesthesia. The Magnetic Resornance Image[MRI] revealed a tumor mass in the thoracic spine that occupied the three colum. The tumor invaded the epidural space of T6 vertebra with compression of the spinal cord. There were no laboratory abnormalities. It was gross totally resected and his neurological symptoms improved. The microscopic examination revealed a plasmacytoma with massive aggregation of histiocytes. Futher neuroradiological studies were carried out and no other lesions were detected.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.63-68
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• 2017

Gaucher disease (GD) is caused by the deficiency of glucocerebrosidase. In pediatric patients with GD, especially Type I GD, enzyme replacement therapy (ERT) can reduce the hepatosplenomegaly and improve the hematologic finding and growth velocity. Herein, we report a 2-year-old girl with Type I GD presented with hepatosplenomegaly, bone pain and growth retardation. A 2 year-old-girl was referred to our hospital due to severe hepatosplenomegaly and growth retardation. She suffered from both leg pain and chronic fatigue. Simple x-ray showed widened distal long bones like that of an 'Erlenmeyer flask' which is associated with GD. The laboratory test showed anemia and thrombocytopenia. The enzyme activity was markedly reduced and the direct sequencing of the GBA gene showed the compound heterozygous mutations, p.G46E and p.L444P. As the G46E have been considered as the protective gene against neuronopathic genotype, we could assess the Type I GD in this patient. After one year of ERT, the growth velocity became 11 cm per year. Bone pain and fatigue disappeared. The volume of liver and spleen was reduced from $683cm^3$ and $703cm^3$ to $590cm^3$ and $235cm^3$, respectively. Although GD is an extremely rare disease in Korea, growth retardation and bone pain in children are the important signs which lead to early detection of GD and a simple radiologic finding is helpful to assess the GD at outpatient clinic. We highlight that the early diagnosis and early ERT is important for good growth and outcome for pediatric patients with GD.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.55-62
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• 2017

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by beta-glucosidase deficiency. An 18 month-old male with hepatosplenomegaly, anemia, thrombocytopenia, and growth retardation referred to our hospital. The patient showed neurological symptoms, such as supranuclear gaze palsy and developmental delay. Bone marrow biopsy performed to rule out malignancy and the results revealed no malignant cell; however, abnormal histiocytes suggesting storage disease was noted. Based on hepatosplenomegaly, bicytopenia and unexplained neurologic manifestations, enzyme activity and genetic analysis were conducted emergently with a strong suspicion of GD. Beta-glucosidase activity in leukocyte was decreased. GBA sequencing to confirm the diagnosis revealed compound heterozygous pathogenic variants (i.e., c.754T>A, c.887G>A), both previously reported as the cause of neuronopathic GD. Under the diagnosis of type 3 GD, the patient immediately received enzyme replacement therapy (ERT). After 17 months of ERT, the size of spleen decreased, and hemoglobin and platelet count returned to normal. In addition, the activity of chitotriosidase and angiotensin converting enzyme decreased. However, myoclonic movement and generalized seizure occurred at the age of 19 months and antiepileptic drug was started. Other neurological deterioration including supranuclear gaze palsy and developmental delay also persisted. A new therapy to overcome neurologic problems should be developed for patients with type 3 GD.