Thoracolumbar Kyphosis in Treated Mucopolysaccharidosis 1 (Hurler Syndrome)

Yasin, Mohammed Naveed; Sacho, Raphael; Oxborrow, Neil; Wraith, J. E.; Williamson, Joseph; Siddique, Irfan

doi:10.1097/brs.0000000000000157

Cited by 28 publications

(20 citation statements)

References 8 publications

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“…This case report highlights the risk of developing further deformity or segmental instability, producing spondylolisthesis below a previously performed instrumented spinal fusion in patients with connective tissue disorders, such as MPS. Patients with MPS may be at particularly high risk of such complications, 16 especially as these patients are normally in severe flexed posture and marked positive sagittal imbalance. 1 The extent of instrumented spinal arthrodesis to correct and stabilize a severe progressive thoracolumbar kyphosis in patients with Hunter syndrome should therefore include 1-2 spinal levels cranial to and caudal to the extent of deformity and avoid a distal fusion beyond the L-4 vertebra in patients with ambulatory capacity.…”

Section: Discussionmentioning

confidence: 99%

“…This case report demonstrates that, in the management of severe thoracolumbar kyphosis associated with Hunter syndrome, satisfactory deformity correction and patient outcomes can be achieved by combined anterior/posterior instrumented arthrodesis, as has been demonstrated previously for other MPS subtypes. 1,5,13,16 Spondylolisthesis is a recognized but infrequent occurrence following fusion for lumbar disc disease, adolescent idiopathic scoliosis, and congenital scoliosis. 2,6,7,9,12,14 To our knowledge, this is the first report of spondylolisthesis developing after instrumented fusion for syndromic kyphoscoliosis, although this may not be unexpected in a patient with MPS.…”

Section: Discussionmentioning

confidence: 99%

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Thoracolumbar kyphoscoliosis with unilateral subluxation of the spine and postoperative lumbar spondylolisthesis in Hunter syndrome

Roberts¹

2016

SPI

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Surgical correction for kyphoscoliosis is increasingly being performed for patients with mucopolysaccharidosis (MPS). Reported case series have predominantly included patients with Type I (Hurler) and Type IV (Morquio) MPS. To their knowledge, the authors describe the first case report of surgical management of thoracolumbar kyphoscoliosis in Hunter syndrome (MPS Type II) and the rare occurrence of lumbar spondylolisthesis following surgical stabilization. A 12-year-old boy with Hunter syndrome presented with severe thoracolumbar kyphoscoliosis and no associated symptoms. Spinal radiographs demonstrated kyphosis of 48° (T11-L3) and scoliosis of 22° (T11-L3) with an anteriorly hypoplastic L-1 vertebra. The deformity progressed to kyphosis of 60° and scoliosis of 42° prior to surgical intervention. Spinal CT scans identified left T12-L1 facet subluxation, causing anterior rotatory displacement of the spine proximal to L-1 and bilateral L-5 isthmic spondylolysis with no spondylolisthesis. A combined single-stage anterior and posterior instrumented spinal arthrodesis from T-9 to L-4 was performed. Kyphosis and scoliosis were corrected to 4° and 0°, respectively. Prolonged ventilator support and nasogastric feedings were required for 3 months postoperatively. At 2.5 years following surgery, the patient was asymptomatic, mobilizing independently, and had achieved a solid spinal fusion. However, he had also developed a Grade II spondylolisthesis at L4–5; this was managed nonoperatively in the absence of symptoms or further deterioration of the spondylolisthesis to the 3.5-year postoperative follow-up visit. Satisfactory correction of thoracolumbar kyphoscoliosis in Hunter syndrome can be achieved by combined anterior/posterior instrumented arthrodesis. The risk of developing deformity or instability in motion segments adjacent to an instrumented fusion may be greater in patients with MPS related to the underlying connective tissue disorder.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thoracolumbar kyphoscoliosis with unilateral subluxation of the spine and postoperative lumbar spondylolisthesis in Hunter syndrome

Roberts¹

2016

SPI

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“…HSCT has shown the most promising results in patients with MPS I, although graft failure remains a significant risk [178, 179]. Following HSCT with successful engraftment, some patients exhibit stabilized, or improved spinal manifestations, but for many the disease continues to progress, often requiring surgical correction [180–182]. Findings for animal models appear similar, with spine disease persisting and/or progressing after HSCT in MPS I cats [183].…”

Section: Treating the Spinal Manifestations Of Mps: Current And Fumentioning

confidence: 99%

Pathogenesis and treatment of spine disease in the mucopolysaccharidoses

Peck

Casal

Malhotra

et al. 2016

Molecular Genetics and Metabolism

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The mucopolysaccharidoses (MPS) are a family of lysosomal storage disorders characterized by deficient activity of enzymes that degrade glycosaminoglycans (GAGs). Skeletal disease is common in MPS patients, with the severity varying both within and between subtypes. Within the spectrum of skeletal disease, spinal manifestations are particularly prevalent. Developmental and degenerative abnormalities affecting the substructures of the spine can result in compression of the spinal cord and associated neural elements. Resulting neurological complications, including pain and paralysis, significantly reduce patient quality of life and life expectancy. Systemic therapies for MPS such as hematopoietic stem cell transplantation and enzyme replacement therapy have shown limited efficacy for improving spinal manifestations in patients and animal models, and there is therefore a pressing need for new therapeutic approaches that specifically target this debilitating aspect of the disease. In this review, we examine how pathological abnormalities affecting the key substructures of the spine – the discs, vertebrae, odontoid process and dura – contribute to the progression of spinal deformity and symptomatic compression of neural elements. Specifically, we review current understanding of the underlying pathophysiology of spine disease in MPS, how the tissues of the spine respond to current clinical and experimental treatments, and discuss future strategies for improving the efficacy of these treatments.

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“…The skeletal abnormalities are collectively known as dysostosis multiplex, and consist of stiffness and contracture of joints, enlarged skull, genu valgum, thoracolumbar kyphosis, hip dysplasia, abnormally shaped vertebrae and ribs, hypoplastic epiphyses and short stature [5], [6], [7], [8]. As a result of the skeletal manifestations, MPS I-H patients typically undergo multiple high-risk surgical interventions to delay the progression of the skeletal disease and improve quality of life [9], [10], [11]. Novel therapeutic treatments such as bone marrow or umbilical cord blood transplantation and weekly enzyme replacement are currently being used to sustain overall enzyme activity and have improved and extended the quality of life of Hurler patients.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the MPS I-H knock-in mouse reveals increased femoral biomechanical integrity with compromised material strength and altered bone geometry

Oestreich

Garcia

Yao

et al. 2015

Molecular Genetics and Metabolism Reports

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Mucopolysaccharidosis type I (MPS I), is an autosomal recessive lysosomal storage disorder caused by a deficiency in the α-L-iduronidase enzyme, resulting in decreased enzymatic activity and accumulation of glycosaminoglycans. The disorder phenotypically manifests with increased urine glycosaminoglycan excretion, facial dysmorphology, neuropathology, cardiac manifestations, and bone deformities. While the development of new treatment strategies have shown promise in attenuating many symptoms associated with the disorder, the bone phenotype remains unresponsive. The aim of this study was to investigate and further characterize the skeletal manifestations of the Idua-W392X knock-in mouse model, which carries a nonsense mutation corresponding to the IDUA-W402X mutation found in Hurler syndrome (MPS I-H) patients. μCT analysis of the microarchitecture demonstrated increased cortical thickness, trabecular number, and trabecular connectivity along with decreased trabecular separation in the tibiae of female homozygous Idua-W392X knock-in (IDUA−/−) mice, and increased cortical thickness in male IDUA−/− tibiae. Cortical density, as determined by μCT, and bone mineral density distribution, as determined by quantitative backscattered microscopy, were equivalent in IDUA−/− and wildtype (Wt) bone. However, tibial porosity was increased in IDUA−/− cortical bone. Raman spectroscopy results indicated that tibiae from female IDUA−/− had decreased phosphate to matrix ratios and increased carbonate to phosphate ratios compared to Wt female tibiae, whereas these ratios remained equivalent in male IDUA−/− and Wt tibiae. Femora demonstrated altered geometry and upon torsional loading to failure analysis, female IDUA−/− mouse femora exhibited increased torsional ultimate strength, with a decrease in material strength relative to Wt littermates. Taken together, these findings suggest that the IDUA−/− mutation results in increased bone torsional strength by altering the overall bone geometry and the microarchitecture which may be a compensatory response to increased porosity, reduced bone tensile strength and altered physiochemical composition.

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Thoracolumbar Kyphosis in Treated Mucopolysaccharidosis 1 (Hurler Syndrome)

Abstract: N/A.

Cited by 28 publications

References 8 publications

Thoracolumbar kyphoscoliosis with unilateral subluxation of the spine and postoperative lumbar spondylolisthesis in Hunter syndrome

Thoracolumbar kyphoscoliosis with unilateral subluxation of the spine and postoperative lumbar spondylolisthesis in Hunter syndrome

Pathogenesis and treatment of spine disease in the mucopolysaccharidoses

Characterization of the MPS I-H knock-in mouse reveals increased femoral biomechanical integrity with compromised material strength and altered bone geometry

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