LAUSR

Dysostosis multiplex is a progressive skeletal disease in patients with mucopolysaccharidosis type I (MPS I). One of its key features is thoracolumbar kyphosis and no guideline for surgical treatment is available yet. Therefore, we investigated the natural course of kyphosis and initiated an international consensus procedure with the aim to develop the first clinical practice guideline for the management of kyphosis in MPS I patients. Sequential radiographs (WKZ/UMC Utrecht and Amsterdam UMC, the Netherlands Royal Manchester Children’s Hospital, United Kingdom San Gerardo Hospital, Italy) were obtained and measurements included the kyphotic angle (modified Cobb angle (CA) and posterior angle (PA), both developed by us for measurement of kyphosis in dysplastic vertebrae) and spondylolisthesis. A modified Delphi procedure was used to develop statements with an international expert panel including 10 spinal/orthopedic surgeons, 6 metabolic pediatricians and 3 physiotherapists, all experienced in MPS I. The procedure consisted of 3 written rounds and a face-to-face meeting. In the natural history study 44 patients (233 radiographs) were included. Intra- and inter-rater reliability was ≥ 0.9 for all measurements. The median modified CA was larger in Hurler patients (38°) compared to non-Hurler patients (9°) and an abnormal modified CA was present at a younger age. A modeled trend showed a progression of the modified CA of 1.8°/year for Hurler patients. The modified CA and the PA correlated strongly. Spondylolisthesis was present in 34 patients. During the modified Delphi procedure 16 statements on decision for surgery and goals of treatment were developed. Consensus was reached on all statements. In conclusion, we present an extensive radiographic assessment of thoracolumbar kyphosis in MPS I patients showing kyphosis is progressive over time. These natural history data may be important for future studies. In addition, we present the first clinical practice guideline for management of kyphosis in MPS I patients.