Journal of Inherited Metabolic Disease

, Volume 34, Issue 3, pp 755–761

The craniocervical junction following successful haematopoietic stem cell transplantation for mucopolysaccharidosis type I H (Hurler syndrome)

  • Elke Miebach
  • Heather Church
  • Alan Cooper
  • Jean Mercer
  • Karen Tylee
  • Robert F. Wynn
  • J. Edmond Wraith
Original Article

DOI: 10.1007/s10545-011-9309-5

Cite this article as:
Miebach, E., Church, H., Cooper, A. et al. J Inherit Metab Dis (2011) 34: 755. doi:10.1007/s10545-011-9309-5

Abstract

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.

Abbreviations

MPS

Mucopolysaccharidosis

H

Hurler

HSCT

Haematopoietic stem cell transplantation

GAG

Glycosaminoglycan

CCJ

Craniocervical junction

MRI

Magnetic resonance imaging

GVHD

Graft versus host disease

ERT

Enzyme replacement therapy

DE

Donor engraftment

EA

Enzyme activity

DS

Dermatan sulphate

CS

Chondroitin sulphate

MMC

Myelomalacia

Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  • Elke Miebach
    • 1
  • Heather Church
    • 2
  • Alan Cooper
    • 2
  • Jean Mercer
    • 2
  • Karen Tylee
    • 2
  • Robert F. Wynn
    • 2
  • J. Edmond Wraith
    • 2
  1. 1.Department of Paediatrics, Children`s Hospital, Johannes Gutenberg-Universität MainzMainzGermany
  2. 2.St Mary’s HospitalManchesterUK