Enzyme Replacement Therapy in Patients Who Have Mucopolysaccharidosis and Are younger than 5 years old

5세 미만 뮤코다당체침착증 환자에서의 효소 대체 요법

  • Park, Seong-Won (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Son, Yeong-Bae (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Se-Hwa (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jo, Seong-Yun (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Ji, Seon-Tae (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jin, Dong-Gyu (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 박성원 (성균관 대학교 의과대학 소아과학교실) ;
  • 손영배 (성균관 대학교 의과대학 소아과학교실) ;
  • 김세화 (성균관 대학교 의과대학 소아과학교실) ;
  • 조성윤 (성균관 대학교 의과대학 소아과학교실) ;
  • 지선태 (성균관 대학교 의과대학 소아과학교실) ;
  • 진동규 (성균관 대학교 의과대학 소아과학교실)
  • Published : 2010.07.10

Abstract

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.

Keywords