Haematopoietic stem cell transplantation (HSCT) for Hurler syndrome
Haematopoietic stem cell transplantation (HSCT) is the current standard of care for children with severe mucopolysaccharidosis type I (Hurler syndrome, MPS I-H) who are diagnosed early and are medically eligible. Donor stem cells provide a long-term source of the missing enzyme, alpha-L-iduronidase (IDUA), and can reach many organs including the brain. When performed in experienced centres and at a young age, HSCT can markedly improve survival and help preserve neurocognitive function compared with the natural history of the disease.
This page explains how HSCT works, when it is recommended, what benefits and risks to expect, and what the transplant journey looks like for children with Hurler syndrome and their families.
What haematopoietic stem cell transplant actually does
HSCT replaces a child’s blood and immune system with stem cells from a healthy donor (bone marrow, peripheral blood or umbilical cord blood). These donor cells:
- Settle in the child’s bone marrow and make new blood cells
- Produce the IDUA enzyme that children with Hurler syndrome cannot make enough of
- Travel through the bloodstream into tissues and the central nervous system, where the enzyme can be taken up by neighbouring cells
Over time, this can reduce storage of glycosaminoglycans (GAGs) in many organs and slow disease progression.
Who is HSCT for – and who it is not for
International consensus and long-term outcome data support HSCT as the preferred treatment for children with:
- Severe MPS I-H (Hurler phenotype)
- Diagnosed before about 2–2.5 years of age
- With sufficient cardiac, respiratory and general health to tolerate transplant
Key factors the team considers:
•Age at diagnosis and speed of progression
•Neurocognitive status at the time HSCT is considered
•Severity of cardiac and respiratory disease
•Availability of a suitable donor and transplant centre experience
Donors, conditioning and engraftment
Donor sources
Several donor types are used successfully in Hurler syndrome:
Matched sibling donor (MSD)
best outcomes when availableMatched unrelated donor (MUD)
commonly usedUnrelated umbilical cord blood
important option, particularly where rapid access is neededModern series using optimised donor selection and protocols report engrafted survival approaching or exceeding 80–90% in experienced centres.
Conditioning
Before HSCT, the child receives myeloablative conditioning (chemotherapy, sometimes with radiotherapy) to:
- ✓ Make space in the bone marrow for donor cells
- ✓ Suppress the immune system to allow engraftment
Choice of regimen varies between centres, aiming to balance engraftment success with short- and long-term toxicity.
What the HSCT process looks like for families
The transplant journey involves several key phases, each with specific goals and care requirements.
Pre-transplant assessment
- Detailed evaluation of heart, lungs, brain, liver/spleen, bones, hearing and vision
- Infection screening, immunisation checks
- Neurodevelopmental assessment
Preparation and central line insertion
- Insertion of a central venous catheter
- Introduction to the transplant ward
- Meeting nursing staff and support services
Conditioning treatment
- Several days of chemotherapy (and possibly other drugs)
- Close monitoring for nausea, mucositis, infections
- Regular organ function checks
Stem cell infusion (day 0)
- Donor stem cells infused like a blood transfusion
- Usually painless procedure
- Child is awake or lightly sedated
Engraftment and early recovery
- Period of very low blood counts with high infection risk
- Transfusions, antibiotics and supportive care as needed
- Engraftment usually occurs within 2–4 weeks
Discharge and early follow up
- Child goes home when stable
- Frequent clinic visits required
- Monitoring of blood counts, chimerism, organ function
Long term follow up
- Gradual spacing of visits
- Ongoing metabolic assessment
- Multidisciplinary care for years
What HSCT can achieve in Hurler syndrome
ERT uses a manufactured form of IDUA, given as a weekly intravenous infusion. The enzyme travels in the bloodstream and is taken up by many cells, helping them break down stored glycosaminoglycans (GAGs).
- Improves survival dramatically compared with untreated natural history
- Can stabilise or partially preserve cognitive development, especially when performed before significant neurocognitive decline
- Reduces hepatosplenomegaly, improves airway obstruction and can improve some cardiac features
- Normalises or substantially improves blood IDUA levels and GAG excretion in many patients
Not a cure – residual disease is common
Long term follow up shows that many children continue to live with residual disease, particularly affecting:
•The skeleton – kyphosis, hip dysplasia, short stature
•Eyes – corneal clouding and visual impairment
•Joints and spine
•Heart valves
Understanding the risks of HSCT
HSCT is a major procedure and carries significant risks, especially in the first year. Important complications include:
- Graft failure or poor engraftment, sometimes requiring a second transplant
- Graft-versus-host disease (GvHD) – donor cells attacking the child's tissues
- Short-term organ toxicity from conditioning (heart, lungs, liver, kidneys)
- Growth disturbance and reduced fertility
- Second malignancy (depending on regimen)
Modern protocols, better donor matching and improved supportive care have reduced transplant-related mortality and improved engrafted survival, but HSCT remains a procedure with non-trivial risk.
Realistic expectations after transplant
Areas where HSCT is most effective
- Survival into adolescence and adulthood
- Slowing or stabilising neurocognitive decline if performed early
- Reducing GAG storage in liver, spleen and many soft tissues
- Improving or stabilising some airway and cardiac manifestations
Areas often only partly improved or unchanged
- Skeletal disease – kyphosis, hip dysplasia, genu valgum, short stature
- Corneal clouding and some forms of visual impairment
- Hearing loss and chronic ENT problems
- Established joint contractures and carpal tunnel syndrome
Many HSCT survivors still require orthopaedic, ENT, ophthalmic and dental surgeries and ongoing therapies throughout childhood and adolescence.
For families: start here
A diagnosis of Hurler syndrome can feel overwhelming. You may be searching for clear explanations, practical advice and honest answers about what happens next. These pages are written in plain language and reviewed by clinicians and families who know MPS I-H well.
Typically started at or soon after diagnosis
Continued until engraftment is secure, then reviewed
Aims to improve clinical condition and reduce GAG burden
Clinical series suggest that peri-transplant ERT is generally safe, does not increase graft failure, and may support better somatic outcomes, though it does not replace the need for HSCT in severe MPS I-H.
How treatment decisions are made today
Questions you can ask your team
You might want to discuss:
- Why HSCT is being recommended (or not recommended) for your child
- What the alternative would be if HSCT is not done
- Which donor type is proposed and why
- Expected short-term risks and risk of transplant-related death in your centre
- What life after HSCT may look like – school, surgeries, long-term medicines
- Whether a second opinion from another transplant or metabolic centre is available
It is completely reasonable to take time, ask for written information and revisit the discussion several times.
Key HSCT principles in MPS I-H
- Treat severe MPS I-H as a time-critical indication: refer promptly once diagnosis and severity are confirmed.
- Early HSCT (ideally <2–2.5 years) in an experienced centre with an appropriate donor offers the best long-term prognosis.
- Consider ERT as bridging therapy and liaise with transplant/metabolic teams regarding timing and peri-transplant management.
- Ensure comprehensive pre-transplant organ assessment (cardiac, respiratory, CNS, skeletal, ENT, ophthalmology) and involvement of multidisciplinary teams early.
- Plan for long-term follow up after HSCT; significant disease burden often persists despite good engraftment, especially in bone, joints and eyes.
Key facts about Hurler syndrome
- HSCT is the standard of care for children with severe MPS I-H diagnosed early and medically fit for transplant.
- Early HSCT can improve survival and help preserve neurocognitive function, but does not completely cure the disease.
- Transplant carries significant risks, which are reduced but not eliminated by modern protocols and experienced centres.
- Many children will still need ongoing surgeries and multidisciplinary care after HSCT, particularly for skeletal, ocular and ENT issues.
- Peri-transplant ERT is often used alongside HSCT to support organ function and reduce disease burden while awaiting engraftment.
What to read next
Current treatments overview
Snapshot of HSCT, ERT and supportive care
Enzyme replacement therapy (ERT)
Laronidase infusions, benefits and limitations
Multidisciplinary care
Cardiac, orthopaedic, respiratory and other specialist follow up
Living with Hurler syndrome
Daily life, education and transition to adulthood after treatment