Current standard of care in Hurler syndrome
Hurler syndrome (severe MPS I, MPS I-H) remains a life limiting multisystem disorder, but outcomes have improved substantially over the past three decades. Haematopoietic stem cell transplantation, usually combined with enzyme replacement therapy and structured multidisciplinary follow up, is now the accepted standard of care for eligible children in many specialist centres. Long term management focuses on optimising survival, preserving neurocognition and function, and limiting residual organ morbidity.
This page summarises current standard of care strategies for Hurler syndrome for clinicians and researchers, drawing together transplant practice, enzyme replacement therapy, and multisystem supportive management, while highlighting areas where practice varies and evidence is still evolving.
This content is intended for healthcare professionals and researchers. It is not a substitute for local protocols, national guidelines or individual patient assessment.
Treatment objectives across the disease course
Key goals in contemporary care of MPS I-H are to:
- Improve survival compared with natural history
- Preserve or stabilise neurocognitive development wherever possible
- Reduce somatic disease burden, particularly cardiac, respiratory and skeletal morbidity
- Minimise treatment related mortality and long term toxicity
- Support growth, function, participation in education and, later, employment
- Maintain quality of life for the child, adult and family
Clinical decision making balances timing and intensity of interventions against disease severity, comorbidities, donor options and family preferences.
Haematopoietic stem cell transplantation in MPS I-H
For most children with a classic Hurler phenotype who are suitable candidates, allogeneic HSCT is considered the primary disease modifying therapy.
Indication and timing
- Indicated in children with a severe MPS I phenotype and evidence of neurocognitive involvement, where transplant related risk is acceptable.
- Best outcomes are seen when HSCT is performed early, typically in the first years of life and ideally before advanced neurocognitive decline.
- Newborn screening programmes, where implemented, support identification of candidates at a pre symptomatic or early symptomatic stage.
Donor sources and conditioning
Current practice often uses:
- Matched related or unrelated bone marrow, peripheral blood or cord blood donors, depending on availability and centre expertise.
- Myeloablative conditioning regimens, adjusted for age and comorbidities, sometimes incorporating serotherapy to reduce graft versus host disease.
- Protocol details vary between centres and countries, and local HSCT teams follow their own evidence based regimens.
Expected benefits and limitations
- HSCT provides donor derived cells that express functional alpha L iduronidase, facilitating cross correction in many tissues and partial correction in the central nervous system.
- Transplant improves survival and stabilises or slows progression of many somatic manifestations.
- CNS benefits are greatest with early transplant, but neurocognitive outcomes still vary.
- Skeletal, valvular and some other manifestations are often only partially modified, so significant residual morbidity is common.
Role of recombinant alpha L iduronidase (ERT)
Recombinant alpha L iduronidase is used in several contexts:
As a bridge to HSCT
- Many centres use ERT prior to transplant to improve somatic condition, reduce organomegaly and potentially lower peri transplant risk.
- Pre transplant ERT is typically continued until conditioning begins, with adjustments around the transplant admission according to local practice.
Long term ERT where HSCT is not performed
- In patients who are not HSCT candidates, or where families decline transplant, long term ERT is used to modify somatic disease.
- ERT can improve or stabilise hepatosplenomegaly, some cardiac and respiratory parameters, and functional endurance.
- CNS disease is not meaningfully modified because current ERT does not cross the blood brain barrier to a significant extent.
Post HSCT ERT
- Some centres continue or reintroduce ERT after HSCT in selected cases, for example where engraftment is suboptimal or specific somatic concerns persist.
- Practice varies and evidence is still emerging.
Structured multisystem care as part of standard management
Even after successful HSCT and/or long-term ERT, Hurler syndrome requires lifelong multidisciplinary surveillance and intervention.
Core team composition
Follow up domains
- Regular assessments of growth, development and neurocognition
- Echocardiography, ECG and cardiac review at defined intervals
- Respiratory function testing and sleep studies where indicated
- Audiology, ENT and ophthalmology surveillance
- Radiological and clinical assessment of spine, hips and limbs
- Monitoring endocrine, nutritional and general health issues
Standard supportive care components
Key elements of supportive care in Hurler syndrome include:
Orthopaedic management
- Monitoring of kyphosis, scoliosis, hip dysplasia and lower limb alignment
- Surgical intervention where indicated, often staged over childhood and adolescence
Airway and respiratory support
- Adenotonsillectomy and other airway surgeries in selected cases
- Management of obstructive sleep apnoea with continuous positive airway pressure or surgery
- Optimisation of chest physiotherapy and management of infections
Cardiac interventions
- Valve surgery for significant regurgitation or stenosis
- Ongoing cardiology input around anaesthesia and pregnancy where relevant
Hearing and vision
- Grommets and hearing aids as needed
- Corneal and other ocular interventions where indicated
Pain and function
- Pharmacological and non pharmacological pain management
- Physiotherapy and occupational therapy to preserve mobility and independence
Standard of care is to treat these issues proactively, integrated with disease modifying therapies.
High risk anaesthesia as a standard planning domain
Children and adults with Hurler syndrome have specific anaesthetic risks due to airway anatomy, skeletal deformity and cardiac and respiratory involvement. Standard care in specialist centres usually includes:
- Preoperative assessment by an anaesthetist experienced in MPS or complex airway disease
- Review of cervical spine stability, cardiac function, respiratory status and previous airway history
- Planning for advanced airway management techniques and backup strategies
- Close post operative monitoring, especially after major orthopaedic or cardiac procedures
- An emergency anaesthetic information summary is often held by families and shared with local hospitals.
Standard care beyond paediatrics
With improving survival, transition to adult care is now an expected part of the pathway for an increasing number of individuals with MPS I-H.
Standard themes include:
- Early preparation and joint paediatric adult clinics where available
- Clear documentation of HSCT history, ERT exposure, cumulative surgical interventions and current organ status
- Identification of adult specialists interested in inherited metabolic disorders, cardiology, respiratory medicine, orthopaedics and rehabilitation
- Support for vocational planning, housing, relationships and reproductive counselling
- Maintenance of surveillance schedules adapted to adult comorbidities
Transition is a process rather than a single transfer, and is now considered integral to standard of care where adult services exist.
Recognising differences in access and implementation
While HSCT and ERT combined with multidisciplinary care represent the standard in many high resource settings, global variability is substantial:
- Newborn screening is not universally implemented, leading to delays in diagnosis.
- Access to HSCT may be limited by geography, infrastructure, donor availability or funding.
- Access to ERT and long term follow up varies widely between countries and health systems.
- Even within well resourced systems, practice can differ regarding timing of HSCT, duration of pre transplant ERT and post transplant strategies.
- Research initiatives and policy work increasingly focus on harmonising care pathways and improving equity of access.
Applying the standard of care to individual patients:
- Has this person been fully evaluated for HSCT eligibility and timing, taking into account neurocognitive status, donor options and comorbidities?
- What is the current and planned role of ERT in their management?
- Which organ systems are most at risk in the short and medium term, and how are they being monitored?
- What is the current burden of procedures and anaesthetics, and how can perioperative risk be minimised?
- Is there a clearly documented long term plan, including transition to adult services where relevant?
- Are the family or adult linked with appropriate patient organisations, psychological support and practical support services?
These questions do not replace formal guidelines, but can help ensure core elements of standard care are considered.
Designing studies against a realistic baseline:
- HSCT plus or minus ERT and structured multidisciplinary follow up is the de facto comparator for many new interventions in MPS I-H.
- Trials and observational studies should define baseline care clearly, including transplant protocols, ERT regimens and supportive care parameters.
- Outcome measures need to reflect domains that are only partially improved by current standard care, such as neurocognition, skeletal morbidity, valve disease and quality of life.
- Long term follow up is critical to interpret whether new approaches add meaningful benefit beyond existing strategies.
- Embedding research within real world care pathways avoids unrealistic comparators and improves external validity.
Key points about current standard of care
- HSCT, usually combined with ERT and delivered in specialist centres, is the central disease modifying therapy for eligible children with Hurler syndrome.
- ERT is used as a bridge to HSCT and as long term therapy where transplant is not undertaken, with mainly somatic benefits.
- Lifelong multisystem follow up and proactive supportive care are integral parts of standard management.
- Anaesthetic risk, orthopaedic burden, cardiac and respiratory complications and neurocognitive outcomes require structured, multidisciplinary planning.
- Survival and outcomes have improved, but residual morbidity and global variation in access underline the need for ongoing research and service development.
What to read next
Research hub
Main research themes in Hurler syndrome
Unmet need
Residual morbidity and quality of life after current treatments
Scientific background
Molecular and cellular mechanisms of MPS I-H
Treatments and care
Patient facing overview of HSCT, ERT and supportive care
Multidisciplinary care
Organ by organ follow up and team structure
Living with Hurler syndrome
Long term life course perspective