Journal of The Korean Society of Inherited Metabolic disease (대한유전성대사질환학회지)

The Korea Society of Inherited Metabolic Disease (대한유전성대사질환학회)
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Clinical Spectrum and Short-term Effects of Enzyme Replacement Therapy for Mucopolysaccharidosis Type II

제2형 뮤코다당증의 임상적 스펙트럼과 효소대치요법의 단기간 효과

  • Cheon, Chong Kun (Division of Pediatric Genetics, Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine) ;
  • Hwu, Wuh-Liang (Department of Pediatrics and Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine)
  • 전종근 (부산대학교 의과대학 부산대어린이병원 소아청소년과학 유전대사과) ;
  • 휴우리앙 (타이완 의과대학 타이완국립대학병원 소아청소년과학 유전의학과)
  • Published : 2018.12.31
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Abstract

Purpose: We aimed to delineate clinical spectrum and short-term effects after enzyme replacement therapy (ERT) for 5 mucopolysaccharidosis type II (MPS II). Methods: Five patients were diagnosed with MPS II by clinical findings, enzyme activity, and genetic testing. Idursulfase was administered by intravenous infusion at a dose of 0.5 mg/kg every week. Observational chart analysis of patients, who underwent systematic investigations more than 12 months after initiation of ERT was done retrospectively. Results: Three patients were classified as having the attenuated type, and 2 patients were classified as having the severe type. The median age at the diagnosis was 9.6 years (range 3.4-26 years). Four different mutations in 5 Korean patients (4 families) with MPS II were identified, among which two were novel mutations (1 small insertion mutation: p.Thr409Hisfs*22, and 1 missense mutation: p.Gly134Glu). Two severe type sibling patients with the same mutation had different clinical manifestation. Urinary glycosaminoglycan excretion decreased within the twelve months of ERT (P=0.043). Liver and spleen volumes showed reductions that were maintained in all patients (P=0.043 and P=0.043, respectively). Improvements were also noted in left ventricular mass index (P=0.042), shoulder flexion (P=0.043), shoulder abduction (P=0.039), knee flexion (P=0.043), elbow flexion (P=0.042), and respiratory distress index (P=0.041). Conclusion: This study demonstrates that Korean patients with MPS II are clinically heterogeneous and indicates that idursulfase is relatively effective in several clinical parameters including heart size and respiratory distress index without infusion-related reactions in patients with MPS II.

목적: 5명의 제2형 뮤코다당증 환자들의 임상적 스펙트럼과 효소대치요법의 단기간 치료 효과에 관해 알아 보고하고자 하였다. 방법: 5명의 환자들은 임상적 소견, 효소활성화 및 유전자검사에 의해 제2형 뮤코다당증으로 진단되었다. 이두설파제는 일주일 간격으로 0.5 mg/kg의 용량으로 정맥주사 주입을 하였으며, 효소대치요법 시작 전 후 12개월 이상 전신평가를 하였으며, 의무기록을 후향적으로 분석하였다. 결과: 3명의 환자들은 경증 유형, 2명의 환자들은 중증 유형의 제2형 뮤코다당증으로 진단되었다. 진단 시 중위연령은 9.6세(범위 3.4-26세)였다. 네 가계 중 다섯 명의 환자에서 4개의 서로 다른 유전자변이가 확인되었으며, 이중 두 개의 변이는 새로운 돌연변이였다(1개의 작은 삽입돌연변이: p.Thr409Hisfs*22, 1개의 과오돌연변이: p.Gly134Glu). 이중 동일한 유전자돌연변이를 지닌 두 명의 중중 유형의 형제 환자들은 서로 다른 임상적 특징들을 보였다. 12개월 간의 효소대치요법 후 소변 글리코사미노글리칸 배출은 유의하게 감소하였다(P=0.043). 간 및 비장의 용적은 모든 환자에서 유의하게 감소하였다(각각 P=0.043, P=0.043). 이외에도 좌심실질량지수(P=0.042), 어깨관절굽힘각도(P=0.043), 어깨관절벌림각도(P=0.039), 무릎관절굽힘각도(P=0.043), 팔꿉관절굽힘각도(P=0.042), 호흡장애지수(P=0.041)가 모두 호전된 소견을 보였다. 결론: 한국인 제2형 뮤코다당증 환자들은 임상적으로 다양한 특징을 보이며, 단기간의 이두설파제 치료는 주사주입관련 이상반응 없이 심장크기, 호흡장애지수를 포함한 여러 임상적 지표들의 호전에 효과적이었다.

Keywords

References

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