Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiences

Objective: Enzyme replacement therapy (ERT), the only approved therapy for infantile-onset Pompe disease (IOPD), had heterogeneous clinical effects due to factors such as severity, age at first treatment, dosage, and dosing regimens. We report the clinical and biochemical outcomes of a cohort of IOP...

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Main Authors: Yin-Hsiu Chien, Wen-Hui Tsai, Chaw-Liang Chang, Pao-Chin Chiu, Yen-Yin Chou, Fuu-Jen Tsai, Siew-Lee Wong, Ni-Chung Lee, Wuh-Liang Hwu
Format: Article
Language:English
Published: Elsevier 2020-06-01
Series:Molecular Genetics and Metabolism Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2214426920300379
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author Yin-Hsiu Chien
Wen-Hui Tsai
Chaw-Liang Chang
Pao-Chin Chiu
Yen-Yin Chou
Fuu-Jen Tsai
Siew-Lee Wong
Ni-Chung Lee
Wuh-Liang Hwu
author_facet Yin-Hsiu Chien
Wen-Hui Tsai
Chaw-Liang Chang
Pao-Chin Chiu
Yen-Yin Chou
Fuu-Jen Tsai
Siew-Lee Wong
Ni-Chung Lee
Wuh-Liang Hwu
author_sort Yin-Hsiu Chien
collection DOAJ
description Objective: Enzyme replacement therapy (ERT), the only approved therapy for infantile-onset Pompe disease (IOPD), had heterogeneous clinical effects due to factors such as severity, age at first treatment, dosage, and dosing regimens. We report the clinical and biochemical outcomes of a cohort of IOPD patients identified through newborn screening, and evaluating the dosage effect. Study design: A retrospective observational study was designed to describe the long-term clinical and biochemical outcomes of a uniform cohort of IOPD patients who have been treated with high-dosage of ERT. Results: Twenty-eight patients received alglucosidase alpha at either the labeled dosage followed by a high dosage (n = 23) or a high dosage exclusively (n = 5). At a median age of 8.3 years (0.8–17.3), 15 patients were walkers, 8 were weak walkers, and 5 were nonwalkers. The three groups exhibited a significant difference in the age of gross motor decline (p < .001). In patients with classical IOPD diagnosed through newborn screening, those late in ERT initiation (p = .006) or late in high-dosage ERT initiation (p = .044) had a higher risk of motor decline. At the latest assessment, both serum creatine kinase (CK) and urinary glucose tetrasaccharide (uGlc4) levels were lowest in the walkers. During follow up, the biomarker levels, once rose, never returned to normal. Conclusion: Low CK and uGlc4 levels were correlated with favorable response to ERT in IOPD patients, although CK may be more fluctuated than uGlc4. High-dose ERT instituted immediately at newborn screening seems to give the best outcome, and a dosage increase is necessary upon – or, even better, before – a rise in biomarker levels.
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spelling doaj.art-5372fb7ce94c44608bea42669b433dde2022-12-21T22:46:24ZengElsevierMolecular Genetics and Metabolism Reports2214-42692020-06-0123Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiencesYin-Hsiu Chien0Wen-Hui Tsai1Chaw-Liang Chang2Pao-Chin Chiu3Yen-Yin Chou4Fuu-Jen Tsai5Siew-Lee Wong6Ni-Chung Lee7Wuh-Liang Hwu8Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pediatrics, Chi Mei Medical Center, Tainan, TaiwanDepartment of Pediatrics, Cathay General Hospital, Hsinchu, Taiwan; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, TaiwanDepartment of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanDepartment of Pediatrics, National Cheng Kung University Hospital, Tainan, TaiwanDepartment of Pediatrics, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Medical Genetics, China Medical University Hospital, China Medical University, Taichung, TaiwanDepartment of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, TaiwanDepartment of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, TaiwanDepartment of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Corresponding author at: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.Objective: Enzyme replacement therapy (ERT), the only approved therapy for infantile-onset Pompe disease (IOPD), had heterogeneous clinical effects due to factors such as severity, age at first treatment, dosage, and dosing regimens. We report the clinical and biochemical outcomes of a cohort of IOPD patients identified through newborn screening, and evaluating the dosage effect. Study design: A retrospective observational study was designed to describe the long-term clinical and biochemical outcomes of a uniform cohort of IOPD patients who have been treated with high-dosage of ERT. Results: Twenty-eight patients received alglucosidase alpha at either the labeled dosage followed by a high dosage (n = 23) or a high dosage exclusively (n = 5). At a median age of 8.3 years (0.8–17.3), 15 patients were walkers, 8 were weak walkers, and 5 were nonwalkers. The three groups exhibited a significant difference in the age of gross motor decline (p < .001). In patients with classical IOPD diagnosed through newborn screening, those late in ERT initiation (p = .006) or late in high-dosage ERT initiation (p = .044) had a higher risk of motor decline. At the latest assessment, both serum creatine kinase (CK) and urinary glucose tetrasaccharide (uGlc4) levels were lowest in the walkers. During follow up, the biomarker levels, once rose, never returned to normal. Conclusion: Low CK and uGlc4 levels were correlated with favorable response to ERT in IOPD patients, although CK may be more fluctuated than uGlc4. High-dose ERT instituted immediately at newborn screening seems to give the best outcome, and a dosage increase is necessary upon – or, even better, before – a rise in biomarker levels.http://www.sciencedirect.com/science/article/pii/S2214426920300379Newborn screeningEarly treatmentEnzyme replacement therapyPompe diseaseDosage
spellingShingle Yin-Hsiu Chien
Wen-Hui Tsai
Chaw-Liang Chang
Pao-Chin Chiu
Yen-Yin Chou
Fuu-Jen Tsai
Siew-Lee Wong
Ni-Chung Lee
Wuh-Liang Hwu
Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiences
Molecular Genetics and Metabolism Reports
Newborn screening
Early treatment
Enzyme replacement therapy
Pompe disease
Dosage
title Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiences
title_full Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiences
title_fullStr Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiences
title_full_unstemmed Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiences
title_short Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiences
title_sort earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile onset pompe disease evidence from real world experiences
topic Newborn screening
Early treatment
Enzyme replacement therapy
Pompe disease
Dosage
url http://www.sciencedirect.com/science/article/pii/S2214426920300379
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