• 대한청각학회지
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• 제25권1호
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• pp.49-54
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• 2021

Type II mucopolysaccharidosis (MPS II) commonly known as Hunter syndrome, is a rare X-linked lysosomal storage disorder caused by iduronate-2-sulfatase deficiency, which in turn causes otorhinolaryngological manifestations, including sensorineural hearing loss (SNHL). Previously, the median survival age of patients with MPS was approximately 13.4 years. However, in the era of enzyme replacement therapy and other multidisciplinary care modalities, the life expectancy has increased. Herein, we report a rare case of an adolescent with MPS II who underwent SNHL treatment with cochlear implantation (CI). Based on unexpected findings of mastoid emissary veins and overgrowth of the vessels around the temporal bone, CI was performed using the transmeatal approach instead of the conventional transmastoid method, to avoid damage to the vessels. The average hearing threshold after CI was 35 dB and no surgical complications were encountered. Adolescent MPS II may present vessel abnormalities, which can reduce the success rate of surgery. In patients with MPS II with SNHL, CI should be performed under careful monitoring of vessel overgrowth. Moreover, with regard to feasibility of CI in adolescent patients with MPS II with SNHL, surgical techniques such as the transmeatal approach should be selected based on adequate assessment of the case.

• Journal of Audiology & Otology
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• 제25권1호
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• pp.49-54
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• 2021

Type II mucopolysaccharidosis (MPS II) commonly known as Hunter syndrome, is a rare X-linked lysosomal storage disorder caused by iduronate-2-sulfatase deficiency, which in turn causes otorhinolaryngological manifestations, including sensorineural hearing loss (SNHL). Previously, the median survival age of patients with MPS was approximately 13.4 years. However, in the era of enzyme replacement therapy and other multidisciplinary care modalities, the life expectancy has increased. Herein, we report a rare case of an adolescent with MPS II who underwent SNHL treatment with cochlear implantation (CI). Based on unexpected findings of mastoid emissary veins and overgrowth of the vessels around the temporal bone, CI was performed using the transmeatal approach instead of the conventional transmastoid method, to avoid damage to the vessels. The average hearing threshold after CI was 35 dB and no surgical complications were encountered. Adolescent MPS II may present vessel abnormalities, which can reduce the success rate of surgery. In patients with MPS II with SNHL, CI should be performed under careful monitoring of vessel overgrowth. Moreover, with regard to feasibility of CI in adolescent patients with MPS II with SNHL, surgical techniques such as the transmeatal approach should be selected based on adequate assessment of the case.

• 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.

• 한국환경보건학회지
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• 제41권5호
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• pp.358-367
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• 2015

Objectives: This study was performed to evaluate the analytical method for PAH metabolites in human urine using enzyme hydrolysis and solid-phase extraction coupled with LC-(ESI)-MS/MS technique. Methods: We employed HPLC tandem mass spectrometry techniques with appropriate pre-treatment for analysis of 16 OH-PAHs in human urine. Samples were hydrolysis by ${\beta}$-flucuronidase/Aryl sulfatase, and target compounds were extracted by solid-phase extraction with a strata-x cartridge. Cross-validation was performed between Eulji University and Green Cross laboratories with 200 human urine samples. Results: The accuracies were between 90.3% and 118.8%, and precisions (relative standard deviations) were lower than 10%. The linearity obtained was satisfying for the 16 OH-PAH compounds, with a coefficient of determination ($r^2$) higher than 0.99. The results of cross-validation at the two organizations were compared by ICC (interclass correlation coefficient) values. The cross-validation results were excellent or good for all compounds. Conclusion: An analytical method was validated for low nanogram levels of 16 OH-PAHs in human urine. Also, satisfying results were obtained for method validation such as accuracy, precision and ICC of cross-validation.

• Clinical and Experimental Pediatrics
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• 제55권11호
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• pp.430-437
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• 2012

Purpose: Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is rare lysosomal storage disorder caused by N-acetylgalactosamine-6-sulfatase (GALNS) deficiency. Only a few MPS IVA cases have been reported in the Korean literature; there is a paucity of research about clinical or radiologic findings for this disorder. Therefore, we studied clinical findings, radiological features, and genetic data of Korean MPS IVA patients for determining factors that may allow early diagnosis and that may thus improve the patients' quality of life. Method: MPS IVA was confirmed via assay for enzymatic activity of leukocytes in 10 patients. The GALNS gene was analyzed. Patients' charts were retrospectively reviewed for obtaining clinical features and evaluated for radiological skeletal surveys, echocardiography, pulmonary function test, and ophthalmologic test results. Result: Nine patients had severe clinical phenotype, and 1 had an intermediate phenotype, on the basis of clinical phenotype criteria. Radiologic findings indicated skeletal abnormalities in all patients, especially in the hips and extremities. Eight patients had an odontoid hypoplasia, and 1 showed mild atlantoaxial subluxation and cord myelopathy. Genetic analysis indicated 10 different GALNS mutations. Two mutations, c.451C>A and c.1000C>T, account for 37.5% (6/16) and 25% (4/16) of all mutations in this samples, respectively. Conclusion: An understanding of the clinical and radiological features involved in MPS IVA may allow early diagnosis of MPS IVA. Adequate evaluations and therapy in the early stages may improve the quality of life of patients suffering from skeletal abnormalities and may reduce life-threatening effects of atlantoaxial subluxation.

• Journal of mucopolysaccharidosis and rare diseases
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• 제5권1호
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• pp.17-21
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• 2021

Hunter syndrome or mucopolysaccharidosis type II (MPS-II) (OMIM 309900) is a rare lysosomal storage disorder caused by deficiency in the activity of the enzyme iduronate-2-sulfatase. This enzyme is responsible for the catabolism of the following two different glycosaminoglycans (GAGs): dermatan sulfate and heparan sulfate. The lysosomal accumulation of these GAG molecules results in cell, tissue, and organ dysfunction. Patients can be broadly classified as having one of the following two forms of MPS II: a severe form and an attenuated form. In the severe form of the disease, signs and symptoms (including neurological impairment) develop in early childhood, whereas in the attenuated form, signs and symptoms develop in adolescence or early adulthood, and patients do not experience significant cognitive impairment. The involvement of the skeletal-muscle system is because of essential accumulated GAGs in joints and connective tissue. MPS II has many clinical features and includes two recognized clinical entities (mild and severe) that represent two ends of a wide spectrum of clinical severities. However, enzyme replacement therapy is likely to have only a limited impact on bone and joint disease based on the results of MPS II studies. The aim of this study was to review the involvement of joints in MPS II.

• Journal of Genetic Medicine
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• 제19권1호
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• pp.32-37
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• 2022

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal disorder caused by the deficiency of arylsulfatase B due to mutations in the ARSB gene. Here, we report the case of a Korean female with a novel variant of MPS VI. A Korean female aged 5 years and 8 months, who is the only child of a healthy non-consanguineous Korean couple, presented at our hospital for severe short stature. She had a medical history of umbilical hernia and recurrent otitis media. Her symptoms included snoring and mouth breathing. Subtle dysmorphic features, including mild coarse face, joint contracture, hepatomegaly, and limited range of joint motion, were identified. Radiography revealed deformities, suggesting skeletal dysplasia. Growth hormone (GH) provocation tests revealed complete GH deficiency. Targeted exome sequencing revealed compound heterozygous mutations in the ARSB genes c.512G>A (p.Gly171Asp; a pathogenic variant inherited from her father) and c.1157C>T (p.Ser386Phe; a novel variant inherited from her mother in familial genetic testing). Quantitative tests revealed increased urine glycosaminoglycan (GAG) levels and decreased enzyme activity of arylsulfatase B. While on enzyme replacement therapy and GH therapy, her height increased drastically; her coarse face, joint contracture, snoring, and obstructive sleep apnea improved; urine GAG decreased; and left ventricular mass index was remarkably decreased. We report a novel variant-c.1157C>T (p.Ser386Phe)-of the ARSB gene in a patient with MPS VI; these findings will expand our knowledge of its clinical spectrum and molecular mechanisms.

• Clinical and Experimental Pediatrics
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• 제51권6호
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• pp.650-654
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• 2008

당원병(GSD)과 점액다당류증(MPS)은 각각 독립된 유전 질환으로, 각기 다른 대사에 관여하는 효소의 결핍으로 인해 전구물질이 축적되어 임상 증상을 나타낸다. 간비대는 두 질환 모두에서 나타나는 중요한 임상 양상이다. 저자들은 이 드문 두 질환이 한 환자에서 동시에 발견되어 이에 보고하고자 한다. 16개월 남아가 2개월 동안 반복적인 중이염을 앓았고, 인근 병원을 다니던 중 우연히 간비대가 발견되었다. 환아는 이마가 튀어나온 조악한 얼굴 모양을 가지고 있었다. 환아의 간은 4횡지 정도로 촉지되었고, 그 성상은 부드럽고 무른 느낌이었으나 경계가 예리하게 만져졌다. 혈액 검사상, AST와 ALT가 85 IU/L, 77 IU/L로 약간 상승되어 있었다. 공복 저혈당은 보이지 않았고, 혈청 젖산, 요산, 콜레스테롤 모두 정상 소견을 보였다. 복부 초음파에서는 간의 메아리 발생 정도(echogenecity)가 증가되어 있었다. 간 생검을 실시하였고, 현미경 검사상 둥근 간세포들이 관찰되었는데, 그 간세포 내에는 Periodic Acid-Schiff 염색에서 진하게 염색되는 거대한 당원 입자들 다수와 이와 동반된 지방 공포(lipid vacuole)가 포함되어 있었다. 전자현미경에서 간세포의 핵과 세포질 모두에 당원 입자들이 포함되어 있었고 거대한 미토콘드리아도 관찰할 수 있었다. 생검을 통해 채취한 간 조직을 분석한 결과, 간의 당원 함량은 9.3%로 정상수치에 비해 증가되어 있었으나, 간의 glucose-6-phosphatase 활성도는 정상이어서 Ia형이 아닌 당원병으로 진단하게 되었다. 한편, X 선상 척추 앞면의 부리모양(beak-shape)와 J 모양의 안장(sella)과 같은 여러 골격의 이상 소견을 보였으며, 소변의 점액다당류 농도 또한 증가되어 있었다. Iduronate sulfatase 활성도가 0.1 nmol/hr/mg protein로 낮은 소견을 보여 헌터 증후군(제2형 점액다당류증, MPS type II)으로 진단할 수 있었다. 이에 저자들은 상기 환자가 당원병과 헌터증후군이 동시에 발견된 첫 환자로 생각되어 보고하는 바이다.

• 한국환경농학회지
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• 제32권4호
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• pp.315-322
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• 2013

BACKGROUND: This study was performed for the identification and quantification of glucosinolate (GSL) contents in seven varieties of rapeseed (Brassica napus L.) sprouts cultivated under dark and light conditions. METHODS AND RESULTS: Crude glucosinolates (GSLs) were desulfated by treating with aryl sulfatase and purified using diethylaminoethyl sepharose (DEAE) anion exchange column. Individual GSLs were quantified using high-performance liquid chromatography (HPLC) with electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Eleven GSLs including six aliphatic (progoitrin, sinigrin, glucoalyssin, gluconapoleiferin, gluconapin, and glucobrassicanapin), four indolyl (4-hydroxyglucobrassicin, glucobrassicin, 4-methoxyglucobrassicin, and neoglucobrassicin) and one aromatic (gluconasturtiin) were identified based on the fragmentation patterns of MS spectrum. Aliphatic GSLs were noted as the predominant group with average 85.2% of the total contents. The most abundant GSLs were progoitrin which was ranged at $8.14-118.68{\mu}mol/g$ dry weight (DW). The highest total GSL amounts were documented in 'Hanra' ($146.02{\mu}mol/g$ DW) under light condition and 'Mokpo No. 68' ($86.67{\mu}mol/g$ DW) in dark condition, whereas the lowest was in 'Tamra' (30.13 and $14.50{\mu}mol/g$ DW) in both conditions. The sum of aliphatic GSLs attributed > 80% in all varieties, except 'Tamra' (67.7% and 64.9% in dark and light conditions, respectively) in the total GSL accumulation. Indolyl GSLs were ranged $2.41-15.73{\mu}mol/g$ DW, accounted 2.78-33.6% of the total GSLs in rapeseed varieties. CONCLUSION(S): These results provide valuable information regarding potential beneficial GSL contents individually. This study attempts to contribute to knowledge of the nutritional properties of the different varieties of rapeseed plants. These results may be useful for the evaluation of dietary information.

• 대한유전성대사질환학회지
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• 제18권2호
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• pp.62-67
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• 2018

헌터증후군이라고 불리는2형 뮤코다당증은 리소좀 축적 질환 중 하나로 이두로네이트 2-설파타제 효소의 기능 저하로 인해 여러 세포와 조직에 글리코사미노글리칸이 축적되어 여러 장기 기능에 부전을 초래하는 선천성 대사질환이다. 헌터증후군은 X 염색체의 장완(Xq28)에 위치하고 있는 IDS 유전자의 변이로 인하여 발생하며 최근까지 350개 이상의 변이가 보고되어 있다. 헌터증후군은 중추 신경계 증상 및 인지 기능 저하 정도에 따라 중증 표현형과 경증 표현형으로 나뉘는데, 표현형은 유전자 변이의 종류와 연관이 있기 때문에 변이를 아는 것은 추후 예후를 예측하는 데에 도움이 된다. 저자들은 최근 항경련제로 조절되지 않는 영아연축으로 내원한 7개월 남에서 엑솜 시퀀싱을 통하여 헌터 증후군을 진단하였다. 환아는 생후 2개월에 난청을 진단 받고 생후 3개월 경 영아연축으로 비가바트린, 프레드니솔론를 복용하였으나 영아연축이 호전되지 않았고, 이에 대한 검사로 시행한 엑솜시퀀싱 상 우연히 반접합체인 어머니로부터 유전된 c.851C>T (p.Pro284Leu) 변이가 발견되었다. 소변을 통한 뮤코다당증 선별 검사인 CPC 검사 결과는 생후 8개월까지 음성이었으나 생후 9개월에는 양성 결과를 보였고, 효소대체요법이 시작된 3개월 이후인 생후 12개월 째에는 다시 음성이 되었다. 생후 15개월인 현재까지 헌터증후군의 특징적인 얼굴 모습이나 간비비대, 관절 구축 등의 증상은 관찰되고 있지 않으며, 조절되지 않는 영아 연축으로 약물 치료를 지속하고 있다. 이를 통하여 환아의 신경학적 증상이 중증 헌터증후군의 임상 증상이 아닌 헌터증후군과 동반된 다른 질환에 의한 것으로 보인다. 저자들은 특징적인 증상이 나타나기 이전인 생후 7개월에 엑솜시퀀싱을 통하여 헌터증후군을 진단하였고 생후 9개월부터 효소대체요법을 시행하여 이에 대해 보고하는 바이다.