Mucopolysaccharidosis type I (MPS-I) is a group of inherited metabolic disorders, of which Hurler’s syndrome (HS) is the most severe subtype. HS, caused by a deficiency of the enzyme α-L-iduronidase, is characterized by progressive neurological deterioration and early death in childhood. For HS, stem cell transplantation (SCT) is the only treatment that is able to prevent disease progression, especially when SCT is performed early in life and before cerebral involvement has occurred. Despite the fact that SCTs for HS are performed for more than 25 years, long term follow-up data are sparse. In addition, there are considerable differences in how health care is organised and provided among the centres.
We are performing an observational cross-sectional European multicentre study. In this study we will evaluate the long term outcome using primary and secondary outcome parameters (table 1) as well as different variables which may influence these outcome parameters (table 2). In addition, the processes of care and quality of life will be evaluated.
The study population will consist of “alive and engrafted” HS patients, transplanted between 1980 and 2005, with a follow up of at least three years. Almost all pediatric transplant centres will participate including the eight most active transplantation centres in Europe (Manchester, London, Dublin, Paris, Lyon, Monza, Prague and Utrecht), accounting for more than 90% of the transplanted HS population registered by the EBMT (European Group for Blood and Marrow Transplantation) registry.
Insight in the long term outcome parameters of successfully transplanted HS patients and the variables influencing these parameters might optimize the selection criteria (whether a patient is eligible for transplantation) and the transplantation techniques used (e.g. stem cell source to use). Furthermore, analysis of the needs and processes of care in patients, parents and family systems can innovate care for HS patients and their parents. This might significantly improve the outcome and quality of life of HS patients and their families.
Additionally, this study will be the basis for a uniform “Europe wide follow up protocol” for Hurler syndrome patients post-SCT. This will make prospective studies for this rare disease possible. Further, the outcome and guideline adaptations may impact SCT for other inborn errors of metabolism as well.
The following people participate in this project:
- JaapJan Boelens (Pediatrician – Immunologist, Wilhelmina Kinderziekenhuis Utrecht)
- Tom de Koning (Pediatrician – Metabolic diseases, Wilhelmina Kinderziekenhuis, Utrecht)
- Ed Wraith (Pediatrician – Metabolic diseases, Royal Manchester Children’s Hospital, Manchester)
- Robert Wynn (Pediatrician – Hemato-oncologist, Royal Manchester Children’s Hospital, Manchester)
- Nico Wulffraat (Pediatrician – Immunologist, Wilhelmina Kinderziekenhuis, Utrecht)
- Mieke Aldenhoven (PhD student, Wilhelmina Kinderziekenhuis, Utrecht)
The project is funded by:
- The Society for Mucopolysaccharide diseases, United Kingdom
- University Medical Centre Utrecht, The Netherlands
| Primary outcome | Secondary outcome |
| Physical characteristic | Endocrinological outcome |
Neuropsychological outcome
Cognitive development
Speech and language
Adaptive skills | Biochemical parameters
Alpha-L-iduronidase activity
Urinary GAG excretion
Chimerism |
| Functional outcome | Work-up
Cerebral/spinal MRI/CT-scan
Abdominal ultrasound/CT-scan |
| Orthopaedic outcome | Quality of life |
| Cardiac outcome | Processes of care |
| Respiratory outcome | Potential new biomarkers (in serum and urine) |
| Ophthalmological outcome | |
| Audiological outcome | |
Patient characteristics
Age at transplantation, genotype, clinical condition at transplantation, etc
Transplantation data
Stem cell source, T-cell depletion, conditioning regimen, GvHD prophylaxis, etc
Complications
Acute GvHD, chronic GvHD, viral reactivation, VOD, IPS, etc
Engraftment
Neutrophil / platelet engraftment
Enzyme activity, urinary GAG excretion (post-SCT), donor chimerism
laatste update: 28-03-2007