J Korean Med Sci.  2008 Apr;23(2):243-250. 10.3346/jkms.2008.23.2.243.

Short-Term Efficacy of Enzyme Replacement Therapy in Korean Patients with Fabry Disease

• Choi JH
• Cho YM
• Suh KS
• Yoon HR
• Kim GH
• Kim SS
• Ko JM
• Lee JH
• Park YS
• Yoo HW

• KMID: 1713456
• DOI: http://doi.org/10.3346/jkms.2008.23.2.243

Abstract

Fabrazyme has been widely used for treatment of Fabry disease since its approval by the U.S. Food and Drug Administration in 2003. This study was undertaken to assess the short-term efficacy and safety of enzyme replacement therapy (ERT) for Fabry disease in Korea. Eight male patients and three female symptomatic carriers aged 13 to 48 yr were included. Fabrazyme was administered by intravenous infusion at a dose of 1 mg/kg every 2 weeks. Plasma and urine globotriaosylceramide (GL-3) levels, serum creatinine, creatinine clearance, and 24-hr urine protein levels were measured every 3 months. Kidney biopsies, ophthalmologic exams, and pure tone audiometry were performed before and 1 yr after ERT. Kidney function, including serum creatinine, creatinine clearance, and the 24-hr urine protein level, remained stable during ERT. Plasma and urine GL-3 levels were reduced within 3 to 6 months of ERT initiation. Microvascular endothelial deposits of GL-3 were decreased from renal biopsy specimens after 1 yr of treatment. The severity of sensorineural hearing loss and tinnitus did not improve after ERT. ERT is safe and effective in stabilizing renal function and clearing microvascular endothelial GL-3 from kidney biopsy specimen in Korean patients with Fabry disease.

Keyword

alpha-galactosidase A; Enzyme Replacement Therapy; Fabry Disease; Globotriaosylceramide; Lysosomal Storage Diseases

MeSH Terms

Adolescent
Adult
Biopsy
Creatinine/blood/urine
Enzymes/*therapeutic use
Fabry Disease/blood/ethnology/*therapy
Female
*Heterozygote
Humans
Korea
Male
Microcirculation
Middle Aged
Trihexosylceramides/blood
alpha-Galactosidase/*therapeutic use

Figure

• 

  Fig. 1 Renal function of patients during enzyme replacement therapy. Serum creatinine (A), creatinine clearance (B), and 24-hr urine protein levels (C) remained stable without aggravation or improvement (p>0.05). Data are presented as mean±SD.

• 

  Fig. 2 Sequential changes in the GL-3 concentration in plasma (A) and urine (B) during enzyme replacement therapy.

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  Fig. 3 Pathologic features before (A, C) and after (B, D) ERT. No significant changes were identified the glomerulus and tubulointerstitium on histologic examination. However, the vascular endothelial GL-3 depositions (arrows) were markedly decreased after the ERT (from patient 1; A and B, PAS staining at ×400 magnification; C and D, toluidine blue staining of semithin sections at ×1,000 magnification).

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