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

Lin HY, Chuang CK, Wang CH, Chien YH, Wang YM, Tsai FJ, Chou YY, Lin SJ, Pan HP, Niu DM, Hwu WL, Ke YY, Lin SP - Mol Genet Metab Rep (2016)

Bottom Line: Five patients had positive effects on cardiac-wall diameters.However, the severity degree of valvular stenosis or regurgitation did not show improvement despite ERT.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

Urinary glycosaminoglycan (GAG) level vs. treatment year for 9 patients with mucopolysaccharidosis VI receiving enzyme replacement therapy for 6.2–11.2 years.
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f0005: Urinary glycosaminoglycan (GAG) level vs. treatment year for 9 patients with mucopolysaccharidosis VI receiving enzyme replacement therapy for 6.2–11.2 years.

Mentions: The diagnosis of MPS VI was confirmed in all 9 patients according to urinary GAG profiles, ASB enzyme activity level, and DNA mutation analysis. The z scores for height and weight at baseline were − 5.4 ± 3.4 and − 1.7 ± 1.3, respectively (Table 1). Seven patients had spinal cord compression symptoms. The baseline clinical assessment data was described as our previous study for these 9 Taiwanese patients with MPS VI in 2010 [28]. After 6.2 to 11.2 years of treatment, there was a 69% decrease in urinary excretion of GAG, indicating biomarker improvement (Table 1, Table 2, Fig. 1). Measures of function also improved, including 6MWT [in 6 patients, mean 150-meter (59%) increase over baseline] and 3MSCT [in 3 patients, mean 60-step (46%) increase]. The time requirement of picking up 10 coins and putting them into a cup in 3 patients decreased 15 s (33%). Shoulder range of motion improved in all 9 patients, as did the Disability Index (0.42 points, 21%). The 4 patients who underwent pulmonary function testing had improved FEV1 by 0.29 L (59%) and FVC by 0.42 L (80%) (Table 1, Table 2). The 5 patients who underwent echocardiographic evaluations had positive effects on cardiac-wall diameters. After ERT, the mean LVMI z score decreased from 3.18 to 1.88, the mean IVSd z score decreased from 6.86 to 2.33, and the mean LVPWd z score decreased from 1.70 to 0.30 (Fig. S1). Four of these 5 patients had improved cardiac diastolic function according to the improvement of E/A ratio (Fig. S2). However, the severity of valvular stenosis or regurgitation remained stable and did not show improvement despite ERT (Fig. S3). Liver and spleen size decreased or remained unchanged after ERT in all 9 patients by abdominal ultrasonographic assessments (Table 3). Three patients who underwent baseline and follow-up DXA screening after receiving ERT for 3.8 to 7.4 years showed an increase in absolute BMD values, as well as an improvement in HAZ adjusted BMD z score (Fig. S4). Three patients who had follow-up PTA after undergoing ventilation tube insertion while receiving ERT for 5.2 to 8.5 years showed improvements in AC and BC of the better ear, as well as a decrease in the air-bone gap (Fig. S5). Growth was not appreciably affected by ERT in all 9 patients assessed. Patient 4 did grow somewhat in height, but none of the patients achieved the third percentile for height (Fig. 2a).


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

Lin HY, Chuang CK, Wang CH, Chien YH, Wang YM, Tsai FJ, Chou YY, Lin SJ, Pan HP, Niu DM, Hwu WL, Ke YY, Lin SP - Mol Genet Metab Rep (2016)

Urinary glycosaminoglycan (GAG) level vs. treatment year for 9 patients with mucopolysaccharidosis VI receiving enzyme replacement therapy for 6.2–11.2 years.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834679&req=5

f0005: Urinary glycosaminoglycan (GAG) level vs. treatment year for 9 patients with mucopolysaccharidosis VI receiving enzyme replacement therapy for 6.2–11.2 years.
Mentions: The diagnosis of MPS VI was confirmed in all 9 patients according to urinary GAG profiles, ASB enzyme activity level, and DNA mutation analysis. The z scores for height and weight at baseline were − 5.4 ± 3.4 and − 1.7 ± 1.3, respectively (Table 1). Seven patients had spinal cord compression symptoms. The baseline clinical assessment data was described as our previous study for these 9 Taiwanese patients with MPS VI in 2010 [28]. After 6.2 to 11.2 years of treatment, there was a 69% decrease in urinary excretion of GAG, indicating biomarker improvement (Table 1, Table 2, Fig. 1). Measures of function also improved, including 6MWT [in 6 patients, mean 150-meter (59%) increase over baseline] and 3MSCT [in 3 patients, mean 60-step (46%) increase]. The time requirement of picking up 10 coins and putting them into a cup in 3 patients decreased 15 s (33%). Shoulder range of motion improved in all 9 patients, as did the Disability Index (0.42 points, 21%). The 4 patients who underwent pulmonary function testing had improved FEV1 by 0.29 L (59%) and FVC by 0.42 L (80%) (Table 1, Table 2). The 5 patients who underwent echocardiographic evaluations had positive effects on cardiac-wall diameters. After ERT, the mean LVMI z score decreased from 3.18 to 1.88, the mean IVSd z score decreased from 6.86 to 2.33, and the mean LVPWd z score decreased from 1.70 to 0.30 (Fig. S1). Four of these 5 patients had improved cardiac diastolic function according to the improvement of E/A ratio (Fig. S2). However, the severity of valvular stenosis or regurgitation remained stable and did not show improvement despite ERT (Fig. S3). Liver and spleen size decreased or remained unchanged after ERT in all 9 patients by abdominal ultrasonographic assessments (Table 3). Three patients who underwent baseline and follow-up DXA screening after receiving ERT for 3.8 to 7.4 years showed an increase in absolute BMD values, as well as an improvement in HAZ adjusted BMD z score (Fig. S4). Three patients who had follow-up PTA after undergoing ventilation tube insertion while receiving ERT for 5.2 to 8.5 years showed improvements in AC and BC of the better ear, as well as a decrease in the air-bone gap (Fig. S5). Growth was not appreciably affected by ERT in all 9 patients assessed. Patient 4 did grow somewhat in height, but none of the patients achieved the third percentile for height (Fig. 2a).

Bottom Line: Five patients had positive effects on cardiac-wall diameters.However, the severity degree of valvular stenosis or regurgitation did not show improvement despite ERT.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus