Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series

https://doi.org/10.1016/j.ymgmr.2016.04.003Get rights and content
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Highlights

  • Nine Taiwanese MPS VI patients treated with weekly intravenous infusions of galsulfase for 6.2 to 11.2 years were reviewed.

  • Long-term ERT was beneficial and safe for Taiwanese patients with MPS VI.

  • Long-term ERT reduced urinary GAG and had positive effects on a wide range of clinical functional assessments.

Abstract

Background

Information regarding the long-term outcome of enzyme replacement therapy (ERT) with recombinant human N-acetylgalactosamine 4-sulfatase (rhASB, galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.) for Taiwanese patients with mucopolysaccharidosis (MPS) VI is limited.

Methods

Nine Taiwanese patients with MPS VI (4 males and 5 females; age range, 1.4 to 21.1 years) treated with weekly intravenous infusions of galsulfase (1.0 mg/kg) in 5 medical centers in Taiwan were reviewed. A set of biochemical and clinical assessments were evaluated annually.

Results

After 6.2 to 11.2 years of galsulfase treatment, 6 patients experienced improvement over baseline in the 6-minute walk test by a mean of 150 m (59% change over time), and 3 patients also increased the 3-minute stair climb test by a mean of 60 steps (46%). In a manual dexterity test, 3 patients decreased the time required to pick up 10 coins and put the coins into a cup by 15 s (33%). Shoulder range of motion in all 9 patients improved, and Joint Pain and Stiffness Questionnaire scores improved by 0.42 points (21%). Four patients showed improved pulmonary function. Five patients had positive effects on cardiac-wall diameters. Four patients had improved cardiac diastolic function. Liver and spleen sizes as measured by abdominal ultrasonography remained the same or decreased in all 9 patients. However, the severity degree of valvular stenosis or regurgitation did not show improvement despite ERT. A mean overall 69% decrease in urinary glycosaminoglycan (GAG) excretion indicated a satisfactory biomarker response.

Conclusions

Long-term ERT was beneficial and safe for Taiwanese patients with MPS VI. This treatment reduced urinary GAG and had positive effects on a wide range of clinical functional assessments including endurance, mobility, joint function, pulmonary function, liver and spleen size, cardiac hypertrophy and diastolic dysfunction.

Abbreviations

MPS
mucopolysaccharidosis
ASB
N-acetylgalactosamine 4-sulfatase
GAG
glycosaminoglycan
ERT
enzyme replacement therapy
Galsulfase
recombinant human N-acetylgalactosamine 4-sulfatase
Z score
standard deviation score
6MWT
6-minute walk test
3MSCT
3-minute stair climb test
FVC
Forced vital capacity
FEV1
forced expiratory volume in 1 s
E/A
ratio between early and late (atrial) ventricular filling velocity
LVMI
left ventricular mass index
IVSd
interventricular septum thickness in diastole
LVPWd
left ventricular posterior wall thickness in diastole
LVM
left ventricular mass
BMD
bone mineral density
HAZ
height-for-age
DXA
dual energy x-ray absorptiometry
PTA
pure-tone audiometry
AC
air conduction
BC
bone conduction
HAQ
Health Assessment Questionnaire
CHAQ
Childhood Health Assessment Questionnaire

Keywords

Cardiac hypertrophy
Diastolic dysfunction
Enzyme replacement therapy
Glycosaminoglycans
Mucopolysaccharidosis VI
Pulmonary function

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