• Journal of mucopolysaccharidosis and rare diseases
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• 제3권1호
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• pp.20-27
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• 2017

Purpose: Mucopolysaccharidosis IV (MPS IV) is a disease characterized by deficient activity of N-acetylgalactosamine-6-sulfatase (GALNS) causing excessive lysosomal storage of keratan sulfate (KS). The identification of the relevant disaccharide units of KS after keratanase II digestion followed by liquid chromatography/tandem mass spectrometry detection (LC-MS/MS) is validated and applicable for the preliminary diagnosis of MPS IV. Methods: A total of 67 urine samples were collected and analyzed from 11 MPS IV patients comprising 10 MPS IVA and one MPS IVB patients, and 56 normal controls. Urinary glycosaminoglycan was first precipitated by the Alcian blue method followed by a digestion of keratanase II. The protonated species of the digested disaccharide products were detected by using multiple reaction monitoring experiment. Results: One particular disaccharide of KS was selected. The transition mass-to-charge (m/z) of the parent ion and its daughter ion after collision was $462.0{\rightarrow}97.0$, whereas the chondrosine used as an internal standard in this assay was m/z $353.9{\rightarrow}73.0$. The results corresponded well with the two-dimensional electrophoresis method. The quantities of urinary KS were significantly raised in confirmed MPS IV patients when comparing with those of normal controls ($170.2{\pm}81.1$ vs. $4.06{\pm}1.92{\mu}g/mL$). Conclusion: The LC-MS/MS method for MPS IVA determination is specific, sensitive, validated, and applicable for urinary KS quantification. This method can be used not only as a first-line biochemistry examination of MPS IVA, but also as an outcome survey after enzyme replacement therapy.

• 대한유전성대사질환학회지
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• 제4권1호
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• pp.18-22
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• 2004

• Journal of mucopolysaccharidosis and rare diseases
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• 제2권1호
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• pp.17-18
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• 2016

Enzyme replacement therapy (ERT) is a well-established means of treating lysosomal storage disease (LSD). However, classical IV infusion based ERT method produces less than ideal results, especially, CNS defects and quality of life in patients. To improve these main problems of parental IV formulation for LSDs, we investigate modified ERT method and evaluated the efficacy in animal model.

• Journal of mucopolysaccharidosis and rare diseases
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• 제1권1호
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• pp.15-18
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• 2015

Biopharmaceuticals, with their ability to treat many unmet needs, are seen as promising medications in diabetes mellitus, growth hormone deficiency, chronic renal failure, cancer, and rheumatoid arthritis. However, almost all biopharmaceuticals should be administrated by injection; IV, IM, and SC. In addition, these treatments are long term, and patients should receive frequent injections for many years. Patient compliance is therefore of critical importance to ensure treatment benefits. Therefore, the goal of drug product development should be focused on improving patient compliance by reducing injection-associated pain as well as stable formulation development. This review will suggest the kinds of factors that should be considered to minimize injection pain with regard to formulation, device, and injection procedures focused on SC injections.

• 대한유전성대사질환학회지
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• 제16권1호
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• pp.24-33
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• 2016

뮤코다당증 6형(Mucopolysaccharidosis type VI)은 ARSB 유전자의 변이로 인하여 dermatan sulfate 대사에 관여하는 arylsulfatase B 효소의 결핍으로 유발되는 상염색체 열성 리소좀 축적 질환이다. 본 연구는 국내에서 뮤코다당증 6형으로 진단된 3명의 환자를 대상으로 하였다 3명의 환자는 최초 진단 시 뮤코다당증 6형의 특징적인 증상인 저신장, 다발성 골형성 부전, 심장 판막 이상 및 각막 혼탁을 보였으며 이후 손목 터널 증후군 및 제한성 폐질환의 양상을 보였다. 모든 환자에서 소변의 GAG (glycosaminoglycan)는 증가되어 있었으며 피부 섬유아세포 또는 백혈구에서 측정한 arylsulfatase B는 모두 감소되어 있었고 중합효소 연쇄반응-염기서열분석법에 의한 ARSB 유전자 검사에서는 c.200T>G (p.Ile67Ser), c.982G>A (p.Gly328Arg), c.571C>T (p.Arg191*), c.1054G>A (p.Asp352Asn)의 이형접합체 돌연변이 및 c.512G>A (p.Gly171Asp) 동형접합체 돌연변이를 발견할 수 있었다. recombinant human Arylsulfatase B (rhASB)를 통한 효소 대체 치료는 2008년부터 국내에서도 허가되었으며 효소대체치료 시행 후 소변 GAG (glyco-saminoglycan)는 감소하였으며 관절 운동 및 지구력은 향상되었다. 그러나 관절 침범 및 각막 혼탁, 심장 및 폐 침범 소견은 호전되지 않았다. 본 연구는 뮤코다당증 6형의 특징적인 증상을 보였으며 생화학적 검사 및 분자유전학적 검사를 통해 뮤코다당증 6형으로 확진된 3명의 환자를 대상으로 시행한 효소대체치료의 효과를 보고하는 바이다.

• 대한유전성대사질환학회지
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• 제10권1호
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• pp.59-66
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• 2010

Enzyme replacement of therapy (ERT) is one of the most promising therapeutic strategies for the treatment of lysosomal storage disorders. ERT is available in three types of Mucopolysaccharidosis (MPS): for MPS I (Aludrazyme$^{(R)}$), MPS II (Elaprase$^{(R)}$) and MPS VI (Naglazyme$^{(R)}$) patients who are over 5 years old. But recently, early diagnosis can be done by expert clinicians and even in prenatal case. We describe the case of ERT under 5 years old MPS patients. Up to June, 2010 in Samsung Medical Center, there are 6patients who were diagnosed as MPS and started ERT under 5 years old. 3 patients were MPS I, 3 patients were MPS II. 2 patient who was diagnosed as MPS I was female and others were male. Their age at diagnosis were 4 to 37month-old (4, 13, 16, 25, 27, 37 month-old) and they are now 9 to 60 month-old (9, 39, 32, 81, 60 month-old). The youngest patient was started ERT at 4 month-old and others were started at their 13 to 49 month-old (13, 29, 27, 28, 49 month-old). First manifested symptoms of patients were macrocephaly, kyphosis and coarse face appearance. Especially, in 2 of them, one was MPS I and the other was MPS II had elder brother with same disease. And the youngest one was diagnosed by the iduronate-2-sulfatase (IDS) gene analysis from chorionic villi sampling. His mother knew that she was a heterozygous carrier of IDS gene mutation because her younger brother died from MPS II. All of them confirmed as MPS by the enzyme assay in leukocytes and fibroblast skin culture. We started ERT with ${\alpha}$-L-iduronidase(Aldurazyme$^{(R)}$) to MPS I and did recombinant human iduronate-2-sulfatase (Elaprase$^{(R)}$) to MPS II patients as recommended dose as over 5 years old. But for MPS II patient who was 4 month old, we started ERT by recombinant human IDS (Elaprase$^{(R)}$) with reduced dose 0.1 mg/kg and increased dose every 2 weeks by 0.1mg/kg up to 0.5mg/kg IV infusion. During ERT, all patients had no adverse effects and the excretion of GAGs were decreased. We have evaluated other clinical symptoms such as liver/ spleen volume, heart function and neurologic evaluation. We describe a successful ERT to MPS I and MPS II patient under 5 years old without any adverse event. It indicates that ERT in young children are well tolerated and that it has several effects which may confer clinical benefits with long-term therapy.