• 대한유전성대사질환학회지
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• 제15권3호
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• pp.160-164
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• 2015

Hunter syndrome(Mucopolysaccharidosis type II, MPS type II) is an X-linked disorder of glycosaminoglycans (GAGs) metabolism caused by an iduronate-2-sulfatase (IDS2) deficiency. A 24-month-old boy visited the department of pediatrics with the chief compliant of chronic purulent rhinorrhea beginning at age one. He had a history of repeated acute otitis media and chronic rhinitis. On physical examination he had a coarse face, enlarged tongue, distended abdomen, joint stiffness, and Mongolian spots at his first visit. The urine GAGs level was elevated at 66.10 mg/mmolCr (reference range, <11.1) and iduronate-2-sulfatase activity in leukocyte was decreased at 0.21 nmol/mg protein/hr (reference range, 18.7-57). Finally with an IDS gene mutational analysis, recombinant known mutation between intron 7 and distal of exon 3 in IDS2 was detected. Recombinant iduronate-2-sulfatase therapy was started without any infusion related reactions. The author highlights the importance of suspecting Hunter syndrome when pediatric patients visit with chronic purulent rhinorrhea which is a common cause of hospital visits for infants and children.

• 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.

• 대한소아치과학회지
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• 제39권4호
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• pp.412-417
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• 2012

뮤코다당증(mucopolysaccharidosis : MPS)은 glycosaminoglycans (GAGs)의 분해에 필요한 라이소좀 효소의 결함으로 인해 야기되는 질병으로 GAGs의 대사산물이 세포의 라이소좀 내에 축적되어 점차적으로 세포, 조직 그리고 기관의 기능 이상을 초래해 육체적, 정신적인 퇴행을 보이며, 심한 경우, 조기에 사망하게 되는 다양한 임상양상을 보이는 질환이다. 임상형은 어떠한 효소가 결핍되느냐에 따라 I형에서 IX형으로 분류한다. 치과적인 증상으로는 맹출 지연, 법랑질 저형성증, 왜소치, 부정교합, 하악 과두의 결함, 치은증식, 그리고 함치성낭 같은 여포성낭이 보고되었다. 뮤코다당증 환자는 심혈관계와 호흡계 기능이 취약하므로 치과 치료를 하는 경우, 전신 상태에 대한 주의사항과 뮤코다당증 환자에서 나타날 수 있는 구강 내 증상에 대해 미리 숙지하고, 의학적으로 환아의 전신 상태 변화에 민감하게 대처해가며 치과 진료를 시행해야 한다. 이 증례는 구강 내 다양한 임상증상을 보이는 제2형 뮤코다당증 환아의 치과 진료 후, 다소의 지견을 얻었기에 이를 보고하는 바이다.

• Journal of mucopolysaccharidosis and rare diseases
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• 제3권1호
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• pp.14-19
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• 2017

Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders caused by the deficiency of specific lysosomal enzymes and subsequent accumulation of substrates. Enzyme deficiency leads to progressive intra-lysosomal accumulation of the incompletely degraded substances, which cause dysfunction and destruction of the cell and eventually multiple organ damage. Patients have a broad spectrum of clinical phenotypes which are generally not specific for some LSDs, leading to missed or delayed diagnosis. Due to the availability of treatment including enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation for some LSDs, early diagnosis is important. ERT products have been approved with optimal outcomes for some LSDs in the recent decades, including Gaucher, Fabry, mucopolysaccharidosis (MPS) I, Pompe, MPS VI, MPS II, and MPS IVA diseases. ERT can stabilize the clinical condition, prevent disease progression, and improve the long-term outcome of these diseases, especially if started prior to irreversible organ damage. Based on the availability of therapy and suitable screening methods in the recent years, some LSDs, including Pompe, Fabry, Gaucher, MPS I, MPS II, and MPS VI diseases have been incorporated into nationwide newborn screening panels in Taiwan.

• Journal of Genetic Medicine
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• 제20권2호
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• pp.60-69
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• 2023

Purpose: Despite enzyme replacement therapy (ERT) and/or allogeneic hematopoietic stem cell transplantation, individuals with mucopolysaccharidosis (MPS) I or II often experience significant growth deficiencies. This study aimed to assess the safety and efficacy of recombinant human growth hormone (hGH) treatment in children diagnosed with MPS I or II. Materials and Methods: A total of nine pediatric patients-four with MPS I and five with MPS II-underwent treatment with ERT and hGH at Samsung Medical Center. Results: The mean hGH dose administered was 0.26±0.03 mg/kg/week. In the MPS I group, three patients showed an increase in height Z-score from -4.09±0.83 to -3.68±0.43 after 1 year of hGH treatment, and to -3.10±0.72 by the end of the hGH regimen. In the MPS II group, while the height Z-score of four patients decreased according to standard growth charts, it improved from 1.61±1.79 to 2.71±1.68 based on the disease-specific growth chart through hGH treatment. Two patients discontinued hGH treatment due to lack of efficacy after 22 and 6 months each of treatment, respectively. No new-onset neurological symptoms or necessity for prosthetic or orthopedic surgery were reported during hGH treatment. Conclusion: This study provides insights into the impact of hGH on MPS patients, demonstrating its potential to reverse growth deceleration in some cases. Further research is needed to explore the long-term effects of hGH on changes in body composition, muscle strength, and bone health in this population.

• Journal of mucopolysaccharidosis and rare diseases
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• 제2권1호
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• pp.1-4
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• 2016

Mucolipidosis type II (MLII; MIM#252500) and type III alpha/beta (MLIIIA; MIM#252600) very rare lysosomal storage disease cause by reduced enzyme activity of GlcNAc-1-phosphotransferase. ML II is caused by a total or near total loss of GlcNAc-1-phosphotransferase activity whether enzymatic activity in patient with ML IIIA is reduced. While ML II and ML III share similar clinical features, including skeletal abnormalities, ML II is the more severe in terms of phenotype. ML III is a much milder disorder, being characterized by latter onset of clinical symptoms and slower progressive course. GlcNAc-1-phosphotransferase is encoded by two genes, GNPTAB and GNPTG, mutations in GNPTAB give rise to ML II or ML IIIA. To date, more than 100 different GNPTAB mutations have been reported, causing either ML II or ML IIIA. Despite development of new diagnostic approach and understanding of disease mechanism, there is no specific treatment available for patients with ML II and ML IIIA yet, only supportive and symptomatic treatment is indicated.

• 대한유전성대사질환학회지
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• 제14권2호
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• pp.178-181
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• 2014

헌터증후군(뮤코다당증 II형)은 글리코사미노글리칸의 분해를 촉매하는 효소인 iduronate-2-sulfatase 결핍에 의해 조직이나 기관의 세포 내 리소좀에 heparin sulfate와 dermatan sulfate 등의 전구물질이 축적되어 퇴행성 병변을 일으키는 유전 질환이다. 현재 효소보충요법을 통해 증상의 호전 및 질병의 진행을 지연시키는 치료가 가능하나, 중추신경계 증상이 발현된 경우 치료가 어려운 한계가 있어, 무엇보다 조기에 의심하고 진단하여 치료를 시작하는 것이 중요하다. 따라서 어린연령에 진단된 환아들의 임상적 특징에 대해 이해하는 것이 필요하며, 이에 저자들은 2.5세의 어린 연령에 진단된 환아를 경험하여 이를 보고하는 바이다.

• Journal of mucopolysaccharidosis and rare diseases
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• 제2권1호
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• pp.27-27
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• 2016

• 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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• 제4권1호
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• pp.11-13
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• 2018

In Malaysia, diagnosis and treatment of patients with mucopolysaccharidoses (MPS) is mainly localized at Hospital Kuala Lumpur, which is the national referral center for rare diseases. To date there are 83 patients diagnosed with MPS in our center, with MPS II being the commonest. The Malaysian National Medicines Policy second edition has a specific section on the orphan drugs which includes recombinant human enzyme for enzyme replacement therapy (ERT) in MPS. So far, National Pharmaceutical Regulatory Agency Malaysia has approved recombinant human enzyme for MPS types I (Loranidase), II (idursulfase), IVA (elosulfase alfa), and VI (Galsufase). Access to Idursulfase beta (another recombinant human enzyme for MPS II) and vestronidase alfa-vjbk (MPS VII) required special authorization on named patient basic. Currently there are 25 patients receiving ERT, 70% of the funding are from Ministry of Health (MOH), the remaining 30% are from various charitable funds and humanitarian programs. Thirteen newly diagnosed patients have to queue for an additional fund. Four patients have been treated with Hematopoietic stem cell transplant. MOH has also published guidelines regarding the patient selection criteria for ERT and treatment monitoring schedule.