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

Abstract

Introduction Mucopolysaccharidosis (MPS) VI or Maroteaux-Lamy syndrome (253200) is an autosomal recessive lysosomal storage disorder caused by deficiency in N -acetylgalactosamine-4-sulfatase (arylsulfatase B). The heterogeneity and progressive nature of MPS VI necessitates a multidisciplinary team approach and there is a need for robust guidance to achieve optimal management. This programme was convened to develop evidence-based, expert-agreed recommendations for the general principles of management, routine monitoring requirements and the use of medical and surgical interventions in patients with MPS VI. Methods 26 international healthcare professionals from various disciplines, all with expertise in managing MPS VI, and three patient advocates formed the Steering Committee group (SC) and contributed to the development of this guidance. Members from six Patient Advocacy Groups (PAGs) acted as advisors and attended interviews to ensure representation of the patient perspective. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with expertise and experience managing patients with MPS VI and the manuscript has been evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers. Results A total of 93 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions. Consensus was reached on all statements after two rounds of voting. The greatest challenges faced by patients as relayed by consultation with PAGs were deficits in endurance, dexterity, hearing, vision and respiratory function. 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 VI 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. Electronic supplementary material The online version of this article (10.1186/s13023-019-1080-y) contains supplementary material, which is available to authorized users.

Critical clinical situations in adult patients with Mucopolysaccharidoses (MPS)

“…Due to intubation during surgery and the accompanying soft tissue manipulation, patients may also be at risk of oedema of the airways. As this is frequently coupled with other respiratory features of MPS, post-surgical observation in an intensive care unit is a key stage of the initial recovery period (32,33), and a place in such a unit should be available for all MPS patients in the 24 hours following surgery. Feeding plans need to adapt as the patient recovers, and individualised physiotherapy requirements should be in place to support the patient's rehabilitation (Supplementary information: Post-surgical care).…”

“…First, the risk of anaphylactic reactions to ERT during sepsis or fever is higher; recommendations for MPS IVA, and safety information for ERT for MPS I state that infusions should be avoided in this acute post-surgical setting as patients may experience sepsis or fever during recovery (32,39). Second, adverse events associated with ERT can include fever and chills (14,32,33), and if ERT were provided soon after surgery, determining the cause of such symptoms as ERT-related or surgery-related would be challenging, leading to difficulties in managing the symptom.…”

“…For example, difficult intubations because of narrowed airways are major factors in deferring complex surgeries(47).Intubation difficulties are estimated to occur in 25% of patients with MPS, so the MDT may wish to take additional steps prior to this procedure to be fully prepared if initial procedures do not go ahead as expected. It should be emphasised that recommendations state that surgical procedures should be carried out by, or under the guidance of, MPS experts in centres with intensive care units, and some clinicians will have to assess if they have the necessary expertise and facilities at their centre to manage the challenges of surgery in patients with MPS(32,33).Coordination of MPS care is particularly important as patients with MPS are at high risk of surgical complications and knowledge of these is the key to optimising each procedure(4,5,21,22). A metabolic specialist should also be involved in decision-making with regard to the potential benefits and risks of surgery.…”

Surgical Management of Spinal Disorders in People with Mucopolysaccharidoses

“…Establishing appropriate surgical indications for spinal disorders in MPS remains a challenge though guidelines of MPS have recently been launched [63,64]. Despite new therapeutic modalities such as ERT/HSCT, which are expected to contribute prolonging the life expectancy of patients with MPS, problems remain regarding musculoskeletal disorders, especially spinal problems.…”

Mucopolysaccharidosis type VI: case report with first neonatal presentation with ascites fetalis and rapidly progressive cardiac manifestation

“…The present case indicates that, in MPS with neonatal presentation, including fetal hydrops, besides MPS VII, clinicians should include MPS VI in the differential diagnosis. This can be an extremely valuable diagnostic clue to an early diagnosis so that specific therapy and management can be implemented [34][35][36].…”