The craniocervical junction following successful haematopoietic stem cell transplantation for mucopolysaccharidosis type I H (Hurler syndrome)
Department of Paediatrics, Children`s Hospital, Johannes Gutenberg-Universität Mainz, Langenbeckstr. 2 in 55131, Mainz, Germany. Journal of Inherited Metabolic Disease
(Impact Factor: 3.37).
03/2011; 34(3):755-61. DOI: 10.1007/s10545-011-9309-5
Mucopolysaccharidosis I Hurler (MPS IH) is a progressive multisystemic disorder caused by alpha-L-iduronidase deficiency. First choice of treatment in MPS IH children is haematopoietic stem cell transplantation (HSCT). The effect of HSCT has been shown to have limited influence on skeletal manifestations by poor penetration of musculoskeletal tissues by the enzyme derived from donor leucocytes. Aim of this study was to investigate the effect of HSCT on the craniocervical junction (CCJ) in Hurler patients. We analysed retrospectively sequential magnetic resonance imaging (MRI) scans of 30 patients with Hurler disease treated by HSCT since 1982 at the Royal Manchester Children's Hospital, UK, in order to determine whether the patients suffer from dens hypoplasia. Results were compared with biochemical and clinical characteristics: Enzyme activity (EA), chimerism, urinary glycosaminoglycan (GAG) excretion and neurological status. Investigations were part of standard clinical procedures. Results are descriptive in presentation. In 26/30 patients a determination of odontoid hypoplasia was feasible. The majority showed a normal dens length and an increase with age. Only 3/26 revealed a dens hypoplasia. One of them had only partial donor engraftment (DE) with reduced EA, one of them suffered from chronic graft versus host disease (GVHD). One patient with only partial DE and reduced EA presented with initial dens hypoplasia until preadolescence but normalized later on. There may be a trend towards lower EA and the occurrence of DH in transplanted MPS patients - perhaps the dosage of enzyme plays a role in the correction of skeletal complications in this patient group. HSCT patients with incomplete DE and therefore lower EAs may require special attention and care.
Available from: Jozef Zustin
- "Skeletal manifestations observed in MPS IH has been known as dysostosis multiplex    , consisting of abnormally shaped vertebrae and ribs, enlarged skull, spatulate ribs, hypoplastic epiphyses, thickened diaphyses, bullet-shaped metacarpals, hip dysplasia, genu valgum, and spinal cord compression . There are several reports on skeletal and growth improvement post- HSCT on MPS I              . With successful engraftment, substantial clinical improvements of joint mobility, coarse facial features, and claw hands were reported . "
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ABSTRACT: Mucopolysaccharidosis type I (MPS I; Hurler Syndrome) is a lysosomal storage disease caused by a deficiency of the enzyme α-L-iduronidase which affects multiple organs such as central nervous system (CNS), skeletal system, and physical appearance. Hematopoietic stem cell transplantation (HSCT) is recommended as a primary therapeutic option at an early stage of MPS I with a severe form to ameliorate CNS involvement; however, no description of pathological improvement in skeletal dysplasia has been investigated to date. We here report a 15-year-old male case with MPS I post-HSCT. This patient received successful HSCT at the age of 2 years and 1 month, followed for over 10 years. His activity of daily living including cognitive performance has been kept normal and the present height and weight are 162 cm and 55 kg. Bone deformity has been still developed, resulting in hemiepiphysiodesis of bilateral medial proximal tibia at 12 years of age and successive arthrodesis of thoraco-lumbar spine at 13 years of age; however, skeletal histopathology from surgical remnants showed substantial improvement in bone lesion with markedly reduced occurrence and cell size of vacuolated cells. After a series of surgical procedures, he became ambulant and independent in daily activity. The levels of GAGs in blood were substantially reduced. In conclusion, this long-term post-HSCT observation should shed light on a new aspect of therapeutic effect associated with skeletal pathology and GAG levels as a biomarker, indicating that HSCT is a primary choice at an early stage for not only CNS but skeletal system in combination of appropriate surgical procedures.
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ABSTRACT: Allogeneic HSCT is performed for a small number of inborn errors of metabolism (IEM). Over the last years, transplantation outcomes have improved in this group of patients as the factors that predicted for poor transplantation outcomes were understood and addressed. The role of transplantation and its potential benefit for an individual patient with a certain IEM is therefore now much better defined. In parallel with improvements in transplantation techniques, other therapies such as pharmacological enzyme replacement therapy (ERT), substrate inhibition, and gene therapy have been developed and are increasingly available to clinicians and their patients. This review covers the following areas: (1) the scientific principles that underpin transplantation in IEM; (2) the variables of the transplantation process itself that predict for successful outcome in terms of engrafted survival after HSCT; (3) the reasons that some apparently phenotypically similar disorders might respond very differently to transplantation therapy; (4) the factors that currently influence the response of a particular patient with a particular disease to allogeneic transplantation, and how these factors might be manipulated in the future to further improve transplantation outcomes in different metabolic illnesses; and (5) how other therapeutic modalities, including ERT, gene therapy, and substrate reduction therapy, might complement and compete with HSCT in the coming years.
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ABSTRACT: MPS represents a group of rare hereditary disorders characterized by multisystem involvement due to intralysosomal GAG accumulation. Among various tissues, both the central and peripheral nervous system are affected in almost all types of the disease. Thus, brain and spinal MR imaging are valuable tools for the assessment of neurologic involvement, and there is evidence that they might be reliable markers demonstrating disease severity and efficacy of treatment options currently used in patients with MPS. We aimed to review the most prominent MR imaging features of patients with MPS, paying attention to the physiopathologic mechanisms responsible for these alterations. Along with the description of neuroimaging findings, existing data in relation to their correlation with the severity of neurologic involvement is discussed, while another topic of great importance is the effect of various therapeutic regimens in the progression of brain and spinal MR imaging alterations. Finally, recent data concerning MR spectroscopy studies in MPS are also critically discussed.
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