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

Mol Genet Metab Rep. 2016 Apr 18:7:63-9. doi: 10.1016/j.ymgmr.2016.04.003. eCollection 2016 Jun.

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.

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