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. 2016 Jul 8;11(1):93.
doi: 10.1186/s13023-016-0470-7.

Musculoskeletal manifestations in mucopolysaccharidosis type I (Hurler syndrome) following hematopoietic stem cell transplantation

Mona Schmidt  1 , Sandra Breyer  2 , Ulrike Löbel  3 , Sinef Yarar  4 , Ralf Stücker  2 , Kurt Ullrich  5 , Ingo Müller  6 , Nicole Muschol  5
Affiliations

Musculoskeletal manifestations in mucopolysaccharidosis type I (Hurler syndrome) following hematopoietic stem cell transplantation

Mona Schmidt et al. Orphanet J Rare Dis. .

Abstract

Background: Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for young Hurler patients. Despite halting of neurocognitive decline and improvement of life expectancy, the beneficial effect on the skeletal system is limited. As orthopedic complications are one of the most disabling factors following HSCT, this points to the need for new treatment strategies. The study summarizes musculoskeletal manifestations in 19 transplanted Hurler patients.

Methods: Data were obtained retrospectively. Patients' charts for physical examinations of the joint range of motion (JROM) of shoulders, elbows, hips and knees were reviewed. Radiographic evaluations of thorax, spine, pelvis and hands were performed. MRI scans of the craniocervical junction were analyzed to determine odontoid hypoplasia and the prevalence of craniocervical stenosis.

Results: Nineteen Hurler patients (10 females, 9 males) with an average age of 8.1 years (range 2.5-23.8) at the latest follow-up, who underwent allogenic HSCT between 1991 and 2012, were assessed after an average follow-up period of 6.4 years (range 0.7-22.5). Seventeen patients achieved long-term engraftment, two developed graft failures. The majority of patients showed a steady state or improvements in the mobility of knees (31 %/63 %), hips (47 %/40 %) and elbows (56 %/38 %). However, shoulder abduction was impaired in ¾ of patients and showed the highest rate of progression (31 %). In patients with graft failure, progressive restrictions in JROM were noted. Assessments of the craniocervical junction by MRI showed stable or improved diameters in 67 % of patients. Correction or stabilization of odontoid hypoplasia was found in 64 %. However thoracolumbar kyphosis, scoliosis, hip dysplasia and genua valga were progressive despite HSCT. At the last follow up, 47 % of patients were partially wheelchair dependent, 10 % wheelchair bound and 25 % regularly experienced pain in the spine, hips and lower extremities due to orthopedic problems.

Conclusion: Joint mobility, odontoid hypoplasia and craniocervical stenosis might stabilize or even improve in Hurler patients following HSCT. However, despite the beneficial effects on some musculoskeletal manifestations, skeletal complications are frequently observed and the overall burden of orthopedic disease is significant. Frequent multi-disciplinary follow-up in a specialized center are essential. Novel therapeutic approaches (e.g. anti-inflammatory drugs) are needed to improve musculoskeletal outcomes.

Keywords: Craniocervical stenosis; Dysostosis multiplex; Hip dysplasia; Hurler syndrome; Mucopolysaccharidosis type I; Musculoskeletal manifestations; Odontoid hypoplasia; Thoracolumbar kyphosis.

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Figures

Fig. 1
Fig. 1
Course of joint mobility in successfully transplanted MPS I patients (n = 17). Change in grade of severity (assessed in categories as mild, moderate severe) of shoulder abduction as well as elbow, hips and knee extension at the last available follow up is presented. The highest percentage of improvement was seen in knees (63 % of patients), hips (40 % of patients) and elbows (38 % of patients)
Fig. 2
Fig. 2
Overall prevalence of orthopedic manifestations at any time point over the course of disease
Fig. 3
Fig. 3
Longitudinal MRI assessments of CCJ diameters. The shortest anterior-to-posterior diameters of the CCJ (vertebrae C1-C3) were assessed on sagittal T2-weighted MRI scans and are shown for each patient separately. The two patients with graft failure (patient 14 and 15) are presented as circles. Dashed straight lines indicate the time of surgical intervention. The straight line represents the start of ERT
See this image and copyright information in PMC

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