. 2019 Jun 13;14(1):137.

doi: 10.1186/s13023-019-1074-9.

Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance

Mehmet Umut Akyol¹, Tord D Alden², Hernan Amartino³, Jane Ashworth⁴, Kumar Belani⁵, Kenneth I Berger⁶, Andrea Borgo⁷, Elizabeth Braunlin⁸, Yoshikatsu Eto⁹, Jeffrey I Gold¹⁰, Andrea Jester¹¹, Simon A Jones¹², Cengiz Karsli¹³, William Mackenzie¹⁴, Diane Ruschel Marinho¹⁵, Andrew McFadyen¹⁶, Jim McGill¹⁷, John J Mitchell¹⁸, Joseph Muenzer¹⁹, Torayuki Okuyama²⁰, Paul J Orchard²¹, Bob Stevens²², Sophie Thomas²², Robert Walker²³, Robert Wynn²⁴, Roberto Giugliani²⁵, Paul Harmatz²⁶, Christian Hendriksz²⁷, Maurizio Scarpa²⁸; MPS Consensus Programme Steering Committee; MPS Consensus Programme Co-Chairs

Collaborators, Affiliations

Affiliations

¹ Department of Otolaryngology, Hacettepe University, Ankara, Turkey.
² Department of Neurosurgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
³ Child Neurology Department, Hospital Universitario Austral, Buenos Aires, Argentina.
⁴ Department of Paediatric Ophthalmology, Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
⁵ Department of Anesthesiology, University of Minnesota, Minneapolis, MN, USA.
⁶ Departments of Medicine and Neuroscience and Physiology, New York University School of Medicine, André Cournand Pulmonary Physiology Laboratory, Bellevue Hospital, New York, NY, USA.
⁷ Orthopaedics Clinic, Padova University Hospital, Padova, Italy.
⁸ Division of Pediatric Cardiology, University of Minnesota, Minneapolis, MN, USA.
⁹ Advanced Clinical Research Centre, Institute of Neurological Disorders, Kanagawa, Japan and Department of Paediatrics/Gene Therapy, Tokyo Jikei University School of Medicine, Tokyo, Japan.
¹⁰ Keck School of Medicine, Departments of Anesthesiology, Pediatrics, and Psychiatry & Behavioural Sciences, Children's Hospital Los Angeles, Department of Anesthesiology Critical Care Medicine, 4650 Sunset Boulevard, Los Angeles, CA, USA.
¹¹ Hand and Upper Limb Service, Department of Plastic Surgery, Birmingham Women's and Children's Hospital, Birmingham, UK.
¹² Willink Biochemical Genetic Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
¹³ Department of Anesthesiology and Pain Medicine, The Hospital for Sick Children, Toronto, Canada.
¹⁴ Department of Orthopedics, Nemours/Alfred I, Dupont Hospital for Children, Wilmington, DE, USA.
¹⁵ Department of Ophthalmology, UFRGS, and Ophthalmology Service, HCPA, Porto Alegre, Brazil.
¹⁶ The Isaac Foundation, Campbellford, Ontario, Canada.
¹⁷ Department of Metabolic Medicine, Queensland Children's Hospital, Brisbane, Australia.
¹⁸ Division of Pediatric Endocrinology, Montreal Children's Hospital, Montreal, QC, Canada.
¹⁹ Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²⁰ Department of Clinical Laboratory Medicine, National Centre for Child Health and Development, Tokyo, Japan.
²¹ Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
²² MPS Society, Amersham, Buckinghamshire, UK.
²³ Department of Paediatric Anaesthesia, Royal Manchester Children's Hospital, Manchester, UK.
²⁴ Department of Paediatric Haematology, Royal Manchester Children's Hospital, Manchester, UK.
²⁵ Department of Genetics, UFRGS, and Medical Genetics Service, HCPA, Porto Alegre, Brazil.
²⁶ UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
²⁷ Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa. chris@fymcamedical.co.uk.
²⁸ Center for Rare Diseases at Host Schmidt Kliniken, Wiesbaden, Germany and Department of Paediatrics University of Padova, Padova, Italy.

PMID: 31196221
PMCID: PMC6567385
DOI: 10.1186/s13023-019-1074-9

Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance

Mehmet Umut Akyol et al. Orphanet J Rare Dis. 2019.

. 2019 Jun 13;14(1):137.

doi: 10.1186/s13023-019-1074-9.

Authors

Affiliations

¹ Department of Otolaryngology, Hacettepe University, Ankara, Turkey.
² Department of Neurosurgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
³ Child Neurology Department, Hospital Universitario Austral, Buenos Aires, Argentina.
⁴ Department of Paediatric Ophthalmology, Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
⁵ Department of Anesthesiology, University of Minnesota, Minneapolis, MN, USA.
⁶ Departments of Medicine and Neuroscience and Physiology, New York University School of Medicine, André Cournand Pulmonary Physiology Laboratory, Bellevue Hospital, New York, NY, USA.
⁷ Orthopaedics Clinic, Padova University Hospital, Padova, Italy.
⁸ Division of Pediatric Cardiology, University of Minnesota, Minneapolis, MN, USA.
⁹ Advanced Clinical Research Centre, Institute of Neurological Disorders, Kanagawa, Japan and Department of Paediatrics/Gene Therapy, Tokyo Jikei University School of Medicine, Tokyo, Japan.
¹⁰ Keck School of Medicine, Departments of Anesthesiology, Pediatrics, and Psychiatry & Behavioural Sciences, Children's Hospital Los Angeles, Department of Anesthesiology Critical Care Medicine, 4650 Sunset Boulevard, Los Angeles, CA, USA.
¹¹ Hand and Upper Limb Service, Department of Plastic Surgery, Birmingham Women's and Children's Hospital, Birmingham, UK.
¹² Willink Biochemical Genetic Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
¹³ Department of Anesthesiology and Pain Medicine, The Hospital for Sick Children, Toronto, Canada.
¹⁴ Department of Orthopedics, Nemours/Alfred I, Dupont Hospital for Children, Wilmington, DE, USA.
¹⁵ Department of Ophthalmology, UFRGS, and Ophthalmology Service, HCPA, Porto Alegre, Brazil.
¹⁶ The Isaac Foundation, Campbellford, Ontario, Canada.
¹⁷ Department of Metabolic Medicine, Queensland Children's Hospital, Brisbane, Australia.
¹⁸ Division of Pediatric Endocrinology, Montreal Children's Hospital, Montreal, QC, Canada.
¹⁹ Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²⁰ Department of Clinical Laboratory Medicine, National Centre for Child Health and Development, Tokyo, Japan.
²¹ Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
²² MPS Society, Amersham, Buckinghamshire, UK.
²³ Department of Paediatric Anaesthesia, Royal Manchester Children's Hospital, Manchester, UK.
²⁴ Department of Paediatric Haematology, Royal Manchester Children's Hospital, Manchester, UK.
²⁵ Department of Genetics, UFRGS, and Medical Genetics Service, HCPA, Porto Alegre, Brazil.
²⁶ UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
²⁷ Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa. chris@fymcamedical.co.uk.
²⁸ Center for Rare Diseases at Host Schmidt Kliniken, Wiesbaden, Germany and Department of Paediatrics University of Padova, Padova, Italy.

PMID: 31196221
PMCID: PMC6567385
DOI: 10.1186/s13023-019-1074-9

Abstract

Introduction: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA.

Methods: Twenty six international healthcare professionals across multiple disciplines, with expertise in managing MPS IVA, and three patient advocates formed the Steering Committee (SC) and contributed to the development of this guidance. Representatives from six Patient Advocacy Groups (PAGs) were interviewed to gain insights on patient perspectives. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with experience managing patients with MPS IVA and the manuscript was evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers.

Results: A total of 87 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) disease-modifying interventions (enzyme replacement therapy [ERT] and haematopoietic stem cell transplantation [HSCT]); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions (including spinal, limb, ophthalmic, cardio-thoracic and ear-nose-throat [ENT] surgeries). Consensus was reached on all statements after two rounds of voting. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance).

Conclusion: This manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS IVA and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps.

Keywords: Anaesthetics; ERT; Elosulfase alfa; Enzyme replacement therapy; HSCT; Haematopoietic stem cell transplantation; MPS IVA; Management guidelines; Morquio a syndrome; Mucopolysaccharidosis; Surgery; VIMIZIM.

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Conflict of interest statement

C Hendriksz; is Owner and Director of FYMCA Medical Ltd.; has conducted consultancy work for Actelion, Amicus, Alexion, Audentes, BioMarin Pharmaceutical Inc., Chiesi, Evidera, Inventiva, GSK, SOBI, Health Care at Home, Sanofi Genzyme, Shire. P Harmatz has conducted consultancy work and/or has received grant support from Alexion, Armagen, BioMarin Pharmaceutical Inc., Chiesi, Denali, Genzyme, Enzyvant, Inventiva, JCR Pharmaceuticals, Orphazyme, Pfizer, PTC Therapeutics, RegenXbio, Sangamo, Shire, SOBI and Ultragenyx. R Giugliani has received consultancy fees, and/or investigator fees, and/or speaker honoraria and/or travel grants to attend scientific meetings from Actelion, Amicus, Armagen, BioMarin, Chiesi, GC Pharma, Inventiva, JCR Pharmaceuticals, Lysogene, RegenxBio, Sanofi Genzyme, Shire, Sobi, and Ultragenyx. M Scarpa has received honoraria, research and travel grants from Alexion, BioMarin Pharmaceutical Inc., Chiesi, Sanofi Genzyme, Shire, Ultragenix and Sangamo. MU Akyol has received speaker honoraria and travel grants from Shire. J Ashworth has received honoraria, travel expenses and a research grant from BioMarin Pharmaceutical Inc. and has received consultancy fees from AbbVie and Inventiva. T Alden has received consultant and honoraria payments from BioMarin Pharmaceutical Inc. and Shire. K Belani was a co-investigator on several studies funded by grants from Lysogene and Shire and has received a travel grant from BioMarin Pharmaceutical Inc. for attendance at an advisory meeting. H Amartino has conducted investigator, speaker and consultant work for Amicus, BioMarin Pharmaceutical Inc., Bluebird Bio, Sanofi Genzyme and Shire. K Berger has received consultancy and honoraria payments from BioMarin Pharmaceutical Inc. and Sanofi Genzyme. Andrea Borgo has received travel grants and honoraria from BioMarin Pharmaceutical Inc., and honoraria from Brains for Brains and Shire. E Braunlin has received speaker and travel grants from BioMarin Pharmaceutical Inc. and Sanofi Genzyme, a research funding from BioMarin Pharmaceutical Inc. and Bluebird Bio and has conducted consultancy work for Ultragenyx. Y Eto has received research grants and honoraria from BioMarin Pharmaceutical Inc., Alexion Pharmaceutical Inc., Sanofi Genzym and Actelion Pharmaceuticals Ltd., and honoraria from Dainippon Sumitomo Inc., Japan Chemical Research and Shire Japan. JI Gold has received honoraria and travel grants from BioMarin Pharmaceutical Inc. A Jester has received honoraria, travel grants, and research funding from BioMarin Pharmaceutical Inc. and funding from Shire for equipment to conduct outcomes assessment. S Jones has conducted investigator, speaker and consultancy work for Alexion, BioMarin Pharmaceutical Inc., Orchard therapeutics, Sanofi Genzyme, Shire and Ultragenyx. C Karsli has nothing to disclose. W MacKenzie has received travel grants and honoraria from BioMarin Pharmaceutical Inc. and has conducted consultancy work for Johnson & Johnson. A McFadyen has received unrestricted educational grants from Alexion, BioMarin Pharmaceutical Inc., Sanofi Genzyme, Shire, and Johnson and Johnson. J McGill has conducted speaker, consultancy, board member work and received travel grants from Actelion, BioMarin Pharmaceutical Inc., Sanofi Genzyme and Shire. He has been an investigator for BioMarin Pharmaceutical Inc. J Mitchell has received research support, advisory board fees, and travel grants from BioMarin Pharmaceutical Inc. and has been involved in the conduct of BioMarin clinical trials. He has also received research funding from Sanofi Genzyme and Shire. He has received consultancy fees from Ultragenyx, BioMarin Pharmaceutical Inc., Sanofi Genzyme and Shire. J Muenzer has conducted consultancy work and/or has received grant support from BioMarin Pharmaceutical Inc., Denali, Green Cross, Eloxx, PTC Therapeutics, RegenXbio, Sangamo, Sanofi Genzyme, Shire and Sobi. T Okuyama has received research grants from BioMarin Pharmaceutical Inc., Green Cross, Sanofi Genzyme, Shire, Orchard Therapeutics, and JCR, and has attended advisory boards for Sanofi Genzyme. He is Principal Investigator for ERT clinical trials for MPS II sponsored by Green Cross and JCR. P Orchard has received honoraria, travel and research support from Sanofi Genzyme, and has received research support from BioMarin Pharmaceutical Inc., Bluebird Bio and Horizon Pharma. B Stevens has received grants for the MPS Society from Sanofi Genzyme, Shire, Sangamo, Regenxbio, BioMarin Pharmaceuticals Inc. and Ultragenyx for direct advocacy, expert meetings, literature and travel. S Thomas has received grants for the MPS Society from Sanofi Genzyme, Shire, Sangamo, Regenxbio, BioMarin Pharmaceuticals Inc., Chiesi and Ultragenyx for direct advocacy, expert meetings, honoraria, literature and travel. DR Marinho has received honoraria and travel grants from BioMarin Pharmaceutical Inc. R Walker has received travel grants, honorarium and payments for consulting work from BioMarin Pharmaceutical Inc., Sanofi Genzyme and Shire. R Wynn has conducted consultancy work for Chimerix, Bluebird Bio and Orchard Therapeutics.

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Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance

Collaborators

Affiliations

Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

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LinkOut - more resources

Full Text Sources

Research Materials

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