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

Abstract

BackgroundInformation 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.MethodsNine 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.ResultsAfter 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.ConclusionsLong-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.

Mucopolysaccharidosis III in Taiwan: Natural history, clinical and molecular characteristics of 28 patients diagnosed during a 21‐year period

“…Short stature in patients with MPS III is not as significant as that in other types of MPS, such as MPS IV, MPS VI, MPS I, and MPS II ( Lin et al, , Lin et al, ). For these 28 patients, the mean z scores for height and weight were −0.47 ± 1.97 and 0.02 ± 1.49, respectively.…”

The relationships between urinary glycosaminoglycan levels and phenotypes of mucopolysaccharidoses

“…Previous studies have shown that ERT for MPS I, II, IVA, and VI can lead to good clearance of urine GAGs and significantly improve a wide range of physiological activities and quality of life (Chuang et al, ; Harmatz, Giugliani, & Schwartz, ; Hendriksz et al, ; Lin et al, ; Lin, Chen, Chuang, et al, ; Lin, Chuang, Wang, et al, ; Muenzer et al, ; Ru et al, ; Wraith et al, ). The DMB ratio can provide useful information to evaluate the effectiveness of ERT from a biochemical point of view; however, it cannot directly reflect the efficacy of DS, HS, or KS degradation after ERT.…”

“…In the present study, 68 patients had available data on the presence of hernia, hepatosplenomegaly, claw hands, coarse face, adenotonsillar hypertrophy, valvular heart disease, joint stiffness, and hypermobile joints. Most of the patients (Chuang et al, 2017;Harmatz, Giugliani, & Schwartz, 2006, 2008Hendriksz et al, 2014Hendriksz et al, , 2016Lin et al, 2005;Lin, Chuang, Wang, et al, 2016;Muenzer et al, 2006;Ru et al, 2013;Wraith et al, 2004). The DMB ratio can provide useful information to evaluate the effectiveness of ERT from a biochemical point of view; however, it cannot directly reflect the efficacy of DS, HS, or KS degradation after ERT.…”

“…The main treatments for MPS disorders include enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (Giugliani, Federhen, & Vairo, 2016). ERT is currently available for MPS I, II, IVA, VI, and VII, and it has been shown to improve endurance, joint mobility, and lung function in patients with MPS (Harmatz et al, 2018;Harmatz, Giugliani, & Schwartz, 2006, 2008Hendriksz et al, 2014Hendriksz et al, , 2016Lin et al, 2005Lin, Chuang, Wang, et al, 2016;Muenzer et al, 2006;Wraith, Clarke, & Beck, 2004). Although these treatments cannot cure the diseases, they can improve or alleviate the progression of the natural course.…”

Genotypic‐phenotypic features and enzyme replacement therapy outcome in patients with mucopolysaccharidosis VI from Turkey

“…Therapeutic options include bone marrow transplantation or enzyme replacement therapy (ERT) with supportive therapy. Long‐term galsulfase ERT was associated with improvements in physical endurance, pulmonary functions, stabilized cardiac function, increased survival, and decreased levels of urinary glycosaminoglycans (uGAGs) together with acceptable side effects were previously reported (Giugliani, Lampe, & Guffon, ; Harmatz et al, , , , , , ; Lin et al, ). Initiation of ERT at an earlier age facilitates better outcomes (Furujo, Kubo, Kosuga, & Okuyama, ; Harmatz et al, ; Horovitz et al, ; McGill et al, ).…”