HSCT and ERT in Hurler syndrome: guidance for healthcare professionals
Haematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are the central disease-modifying treatments for Hurler syndrome (severe MPS I, MPS I-H). When used in a timely and coordinated way, they can improve survival and stabilise or slow neurocognitive decline, while modifying somatic disease. However, both carry important risks and limitations, and require close collaboration between metabolic, transplant and multidisciplinary teams.
This page summarises practical, evidence-informed guidance on the roles of HSCT and ERT in MPS I-H, focusing on indications, timing, peri-transplant use of ERT, and long-term management when HSCT is not undertaken.
For healthcare professionals only. This page complements, but does not replace, national and local protocols or discussion with a recognised metabolic and transplant centre.
What HSCT and ERT aim to achieve
In classic Hurler syndrome, the primary goal of treatment is to preserve life and optimise neurocognitive outcome, while limiting somatic disease and treatment-related morbidity. HSCT and ERT are used to:
- Provide a durable source of alpha-L-iduronidase (HSCT)
- Reduce GAG storage and improve somatic manifestations (HSCT ± ERT)
- Stabilise or slow neurocognitive decline, especially when intervention is early
- Improve quality of life, function and long-term survival
Key concepts:
- HSCT is generally the preferred disease-modifying treatment in children with confirmed MPS I-H who are fit for transplant.
- ERT is used as a bridge to HSCT, and as long-term therapy in those who are not transplanted or who have residual disease.
What HSCT and ERT aim to achieve
In classic Hurler syndrome, the primary goal of treatment is to preserve life and optimise neurocognitive outcome, while limiting somatic disease and treatment-related morbidity. HSCT and ERT are used to:
- Provide a durable source of alpha-L-iduronidase (HSCT)
- Reduce GAG storage and improve somatic manifestations (HSCT + ERT)
- Stabilise or slow neurocognitive decline, especially when intervention is early
- Improve quality of life, function and long-term survival
HSCT is generally the preferred disease-modifying treatment in children with confirmed MPS I-H who are fit for transplant.
ERT is used as a bridge to HSCT and as long-term therapy in those who are not transplanted or who have residual disease.
Clinical overview for HCPs — Unmet need →
Who should be considered for HSCT?
Indications vary slightly between centres and guidelines, but common features of HSCT-eligible MPS I-H include:
Typical candidates:
- Confirmed MPS I-H phenotype
- Very low or absent alpha-L-iduronidase activity
- Biallelic IDUA variants consistent with severe disease
- Early onset multisystem involvement and neurocognitive vulnerability
- Age typically in early childhood (infants and toddlers)
- Sufficient cardiac, respiratory and general status for conditioning
Relative contraindications / higher-risk scenarios:
- Advanced neurocognitive decline at presentation
- Severe, uncorrectable cardiac or respiratory disease
- Major comorbidities or organ dysfunction increasing transplant risk
- Borderline cases require MDT discussion and family-centred decision making
MPS I spectrum — Diagnostic algorithms (HCPs) →
Why early referral and decision making matter
Timing strongly influences neurocognitive and survival outcomes. Key principles:
- Earlier is generally better, ideally before marked neurocognitive decline
- In newborn screening regions, prompt referral after confirmation is essential
- Completion of baseline organ assessments
- Donor identification and work-up
- Pre-HSCT optimisation (respiratory, nutritional, dental, ENT)
How enzyme replacement fits around HSCT
Enzyme replacement therapy plays a critical role at different stages of HSCT treatment.
ERT as bridge to HSCT
- Stabilise ERT after diagnosis and before HSCT to improve somatic disease
- To potentially reduce peri-transplant risk in some children
- Follow licensed product information and local protocols
Around the time of transplant
- Some centres pause ERT around conditioning and early engraftment
- Others may continue ERT until stable engraftment
- Decisions made jointly by metabolic and transplant teams
- Clearly communicated to the family
ERT after HSCT
- Many centres discontinue ERT once stable donor engraftment achieved
- ERT reconsidered if graft failure or mixed chimerism with low enzyme levels
- Considered if significant ongoing somatic disease felt ERT responsive
Long-term ERT-focused strategies
HSCT may not be undertaken because of late diagnosis, high transplant risk, family preference, or lack of access to transplant facilities.
- Long-term ERT to reduce somatic burden (organomegaly, cardiac, respiratory, musculoskeletal)
- Intensive multidisciplinary supportive care
- Careful neurodevelopmental and educational support
Set realistic expectations regarding what ERT can and cannot achieve.
Revisit decisions periodically, particularly if new therapies or trials become available.
Baseline assessments before transplant
Typical pre-HSCT work-up includes comprehensive multidisciplinary evaluation:
Organ Assessments
- ✓ Donor searching and HLA typing
- ✓ Immunisation review in line with transplant protocols
- ✓ Detailed discussion with family on procedure, risks and long-term follow-up