Journal of Pediatric Rehabilitation Medicine - Volume 3, issue 2

Article Type: Other

DOI: 10.3233/PRM-2010-0121

Citation: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 83-84, 2010

Authors: Simonaro, Calogera M.

Article Type: Research Article

Keywords: Mucopolysaccharidoses, cartilage, inflammation

DOI: 10.3233/PRM-2010-0120

Citation: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 85-88, 2010

Authors: Decker, Celeste | Yu, Zi-Fan | Giugliani, Roberto | Schwartz, Ida Vanessa D. | Guffon, Nathalie | Teles, Elisa Leão | Miranda, M. Clara Sá | Wraith, J. Edmond | Beck, Michael | Arash, Laila | Scarpa, Maurizio | Ketteridge, David | Hopwood, John J. | Plecko, Barbara | Steiner, Robert | Whitley, Chester B. | Kaplan, Paige | Swiedler, Stuart J. | Conrad, Susan | Paul Harmatz for the MPS VI Study Group,

Article Type: Research Article

Abstract: Background and Methods: Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to …determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. Results: Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16~years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96~weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty. Conclusion: Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation. Show more

Keywords: Mucopolysaccharidosis VI, N$-acetylgalactosamine 4-sulfatase, arylsulfatase B, enzyme replacement therapy, glycosaminoglycans, growth, puberty

DOI: 10.3233/PRM-2010-0113

Citation: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 89-100, 2010

Authors: White, Klane K | Hale, Susan | Goldberg, Michael J

Article Type: Research Article

Abstract: Musculoskeletal disease is a significant burden for children with Mucopolysaccharide (MPS) disorders. The Pediatric Outcomes Data Collection Instrument (PODCI) is a validated, functional measure of musculoskeletal health in children with disabilities. The goal of this study is to describe the musculoskeletal manifestations of children with MPS II (Hunter syndrome), and their functional response to intravenous enzyme replacement therapy (ERT). Patients with MPS II were prospectively entered into an IRB approved registry. Chart …review of physical findings including, shoulder, elbow, hip, knee and ankle range of motion, and need for carpal tunnel release was performed. Radiographs of the spine and pelvis were evaluated in all patients. Serial PODCI exams were administered to all patients. Seven patients, 5 receiving ERT, were included. Four patients had spinal deformities, seven had modest hip disease, and two required carpal tunnel release. PODCI scores were abnormally low in all domains, but significant improvements in PODCI scores were documented with enzyme replacement therapy. Spine and hip deformity are ubiquitous in MPS II, none of which have required surgical intervention, but require long term monitoring. Patients with MPS II should be monitored for carpal tunnel syndrome. Functional improvements are seen, as documented by the PODCI, in children with MPS II on ERT. Show more

Keywords: Hunter syndrome, mucopolysaccharidosis, PODCI, hip, spine

DOI: 10.3233/PRM-2010-0112

Citation: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 101-107, 2010

Authors: Lachman, Ralph | Martin, Kenneth W. | Castro, Sérgio | Basto, Margarida Ayres | Adams, Alexandra | Teles, Elisa Leão

Article Type: Research Article

Abstract: The mucopolysaccharidoses (MPS) represent a group of inheritable, clinically heterogeneous lysosomal storage disorders, in which progressive accumulation of glycosaminoglycans (GAGs) can affect organs and tissues all over the body. The current paper discusses the skeletal X-ray and neuroimaging findings in MPS patients, and the imaging techniques that can be used for diagnosing and monitoring abnormalities in the skeleton and central nervous system. Most MPS types show a typical radiologic expression, called dysostosis …multiplex, which manifests as malformations of the skeletal system involving bones in the skull, thorax, spine, pelvis, long bones, and hands. Abnormalities of the spine and GAG deposits in the meninges surrounding the spinal cord can result in spinal cord compression, which, if untreated, can lead to compressive myelopathy. Magnetic resonance imaging (MRI) is the most powerful imaging technique for detecting spinal cord compression, but also radiography and computed tomography are useful. GAG deposits in the brain and surrounding tissues can result in brain anomalies, i.e. white matter lesions, brain atrophy, and hydrocephalus, which can be detected using MRI. Skeletal X-ray and neuroimaging findings can play an important role in diagnosis, follow-up, surgical or medical planning, and assessment of treatment response in MPS patients. There is a need for standardized procedures in evaluating and monitoring neurologic complications in these patients. Show more

Keywords: Brain diseases, diagnostic imaging, dysostosis multiplex, mucopolysaccharidoses, spinal cord compression

DOI: 10.3233/PRM-2010-0115

Citation: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 109-118, 2010

Authors: McDonald, Arline | Steiner, Robert | Kuehl, Kerry | Turbeville, Sean

Article Type: Research Article

Abstract: Increased functional capacity of major organ systems improves the quality of life and contributes to reductions in the morbidity associated with chronic debilitating diseases. Routine endurance tests can be used to gauge the progression of disease and the impact of therapeutic modalities in disorders with multiple organ system involvement such as with Mucopolysaccharidosis type VI (MPS VI). MPS VI is a progressive disorder affecting multiple organs and tissues due to the deficient activity of …N-acetylgalactosamine-4-sulfatase leading to the accumulation of glycosaminoglycan (GAG) dermatan sulfate. Since 2005, enzyme replacement therapy (ERT) with human recombinant N-acetylgalactosamine-4-sulfatase (galsulfase) has been an available treatment option for MPS VI. These patients are routinely evaluated for extent of disability, disease progression and the impact of ERT. Evaluations are made by a combination of urinary GAG measurement and submaximal intensity endurance tests such as the 3-minute stair climb (3-MSC), and the 6- and 12-minute walk tests (6-MWT and 12-MWT). This review highlights the clinical validity of endurance measures as inexpensive diagnostic tools for diseases affecting multiple organ systems and evaluating the impact of therapeutic modalities, such as ERT for MPS VI. Show more

Keywords: Mucopolysaccharidosis, Maroteaux-Lamy Syndrome, enzyme replacement therapy, glycosaminoglycan, endurance tests, quality of life

DOI: 10.3233/PRM-2010-0114

Citation: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 119-127, 2010

Authors: Alliston, Tamara

Article Type: Research Article

Abstract: Mucopolysaccharidosis type VI (MPS VI), also called Maroteaux-Lamy syndrome, is an autosomal recessive lysosomal storage disorder caused by deficiency of a specific enzyme required for glycosaminoglycan catabolism. Deficiency in the N-acetylgalactosamine-4-sulfatase (4S) enzyme, also called arylsulfatase B (ARSB), may have profound skeletal consequences. In MPS VI, partially degraded glycosaminoglycans (GAGs) such as dermatan sulfate and chondroitin sulfate accumulate within lysosomes. Through mechanisms that remain unclear, the abnormal GAG metabolism impacts several aspects …of cellular function, particularly in the growth plate. This article explores the hypothesis that accrued partially degraded GAGs may contribute to deregulation of signaling pathways that normally orchestrate skeletal development, with a focus on members of the transforming growth factor-β (TGF-β) family. Understanding the molecular mechanisms disrupted by MPS VI may yield insight to improve the efficacy of MPS VI therapies, including bone marrow transplantation and enzyme replacement therapies. Show more

Keywords: MPS VI, TGF-β, chondroitin sulfate, growth plate, osteoblast and chondrocyte differentiation

DOI: 10.3233/PRM-2010-0117

Citation: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 129-138, 2010

Authors: Wilson, Susan | Brömme, Dieter

Article Type: Research Article

Abstract: Cathepsin K, a papain-like cysteine protease, is highly expressed in osteoclasts and plays a critical role in bone resorption. Dysfunction of the enzyme leads to various skeletal abnormalities. The recent knowledge that the collagenolytic activity of cathepsin K depends on interactions with bone and cartilage-resident glycosaminoglycans (GAGs) may shed some light on diseases such as mucopolysaccharidoses (MPSs). MPSs are a group of lysosomal storage diseases characterized by the accumulation of GAGs in tissues including bone. …Typical pathological features of these diseases include skeletal abnormalities such as dysostosis multiplex, short stature, and multiple irregularities in bone development. We describe how further investigation of the cathepsin K/GAG complexes could provide valuable insights into the bone pathology associated with MPS diseases. In this review, we discuss the inhibition of osteoclast function through altered activity of cathepsin K by GAGs and offer insight into a mechanism for the bone pathology seen in MPS patients. Show more

Keywords: Cathepsin K, chondroitin sulfate, cartilage, collagen, glycosaminoglycan, mucopolysaccharidoses, osteoclast

DOI: 10.3233/PRM-2010-0116

Citation: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 139-146, 2010

Article Type: Other

DOI: 10.3233/PRM-2010-0118

Citation: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 147-150, 2010

Article Type: Other

DOI: 10.3233/PRM-2010-0119

Citation: Journal of Pediatric Rehabilitation Medicine, vol. 3, no. 2, pp. 151-152, 2010