Variable disease progression after successful stem cell transplantation: Prospective follow‐up investigations in eight patients with Hurler syndrome

Grigull, Lorenz; Sykora, Karl‐Walter; Tenger, Andreas; Bertram, Harald; Meyer-Marcotty, Max; Hartmann, Hans; Bültmann, Eva; Beilken, Andreas; Zivicnjak, Miroslaw; Mynarek, Martin; Osthaus, A.; Schilke, Reinhard; Kollewe, Katja; Lücke, Thomas

doi:10.1111/j.1399-3046.2011.01595.x

Cited by 20 publications

(11 citation statements)

References 20 publications

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“…However, several studies have reported that subsequent cognitive deterioration occurs after stem cell transplantation, justifying the use of intrathecal enzyme replacement therapy to prevent further decline. 32,33 Our results suggest that the decline in IQ observed in some cases may be due to sequelae of early brain injury due to accumulation of glycosaminoglycans. Patients who were younger than 9 months at the time of transplantation had minimal injury and were still cognitively normal; thus, transplantation of stem cells to supply the missing enzyme prevented further injury.…”

Section: Discussionmentioning

confidence: 70%

Early treatment is associated with improved cognition in Hurler syndrome

Poe

Chagnon

Escolar

2014

Annals of Neurology

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Section: Discussionmentioning

confidence: 70%

Early treatment is associated with improved cognition in Hurler syndrome

Poe

Chagnon

Escolar

2014

Annals of Neurology

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“…HSCT cannot prevent or stabilize progression of the hip abnormalities in most patients [3,17,18,29]. Although data on the long-term follow-up of transplanted MPS I-H patients are very limited, the radiological characteristics, such as (sub)luxation of the hips and decreased articular cartilage, suggest that hip dysplasia may ultimately result, at least in a subgroup of patients, in pain and loss of function.…”

Section: Resultsmentioning

confidence: 99%

Treatment of hip dysplasia in patients with mucopolysaccharidosis type I after hematopoietic stem cell transplantation: results of an international consensus procedure

Langereis

Borgo

Crushell

et al. 2013

Orphanet J Rare Dis

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BackgroundMucopolysaccharidosis type I (MPS-I) is a lysosomal storage disorder characterized by progressive multi-organ disease. The standard of care for patients with the severe phenotype (Hurler syndrome, MPS I-H) is early hematopoietic stem cell transplantation (HSCT). However, skeletal disease, including hip dysplasia, is almost invariably present in MPS I-H, and appears to be particularly unresponsive to HSCT. Hip dysplasia may lead to pain and loss of ambulation, at least in a subset of patients, if left untreated. However, there is a lack of evidence to guide the development of clinical guidelines for the follow-up and treatment of hip dysplasia in patients with MPS I-H. Therefore, an international Delphi consensus procedure was initiated to construct consensus-based clinical practice guidelines in the absence of available evidence.MethodsA literature review was conducted, and publications were graded according to their level of evidence. For the development of consensus guidelines, eight metabolic pediatricians and nine orthopedic surgeons with experience in the care of MPS I patients were invited to participate. Eleven case histories were assessed in two written rounds. For each case, the experts were asked if they would perform surgery, and they were asked to provide information on the aspects deemed essential or complicating in the decision-making process. In a subsequent face-to-face meeting, the results were presented and discussed. Draft consensus statements were discussed and adjusted until consensus was reached.ResultsConsensus was reached on seven statements. The panel concluded that early corrective surgery for MPS I-H patients with hip dysplasia should be considered. However, there was no full consensus as to whether such a procedure should be offered to all patients with hip dysplasia to prevent complications or whether a more conservative approach with surgical intervention only in those patients who develop clinically relevant symptoms due to the hip dysplasia is warranted.ConclusionsThis international consensus procedure led to the construction of clinical practice guidelines for hip dysplasia in transplanted MPS I-H patients. Early corrective surgery should be considered, but further research is needed to establish its efficacy and role in the treatment of hip dysplasia as seen in MPS I.

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“…The canine model of MPS VII has a missense mutation (R166H) in the GUSB gene [8] and closely resembles the disease seen in humans [Online Mendelian Inheritance in Man (OMIM#253220)]. Current treatments for some types of MPS such as hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) have not prevented cardiac disease [3, 9-10]. Gene therapy is being tested in animals with MPS [11].…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of mitral valve disease in mucopolysaccharidosis VII dogs

Bigg

Baldo

Sleeper

et al. 2013

Molecular Genetics and Metabolism

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Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs) in lysosomes and multisystemic disease with cardiavascular manifestations. The goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical signal for structurally-intact collagen in the MV at 6 months of age, when mitral regurgitation had developed. Electron microscopy demonstrated that collagen fibrils were of normal diameter, but failed to align into large parallel arrays. mRNA analysis demonstrated a modest reduction in the expression of genes that encode collagen or collagen-associated proteins such as the proteoglycan decorin which helps collagen fibrils assemble, and a marked increase for genes that encode proteases such as cathepsins. Indeed, enzyme activity for cathepsin B (CtsB) was 19-fold normal. MPS VII dogs that received neonatal intravenous injection of a gamma retroviral vector had an improved signal for structurally-intact collagen, and reduced CtsB activity relative to that seen in untreated MPS VII dogs. We conclude that MR in untreated MPS VII dogs was likely due to abnormalities in MV collagen structure. This could be due to upregulation of enzymes that degrade collagen or collagen-associated proteins, to the accumulation of GAGs that compete with proteoglycans such as decorin for binding to collagen, or to other causes. Further delineation of the etiology of abnormal collagen structure may lead to treatments that improve biomechanical properties of the MV and other tissues.

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Variable disease progression after successful stem cell transplantation: Prospective follow‐up investigations in eight patients with Hurler syndrome

Cited by 20 publications

References 20 publications

Early treatment is associated with improved cognition in Hurler syndrome

Early treatment is associated with improved cognition in Hurler syndrome

Treatment of hip dysplasia in patients with mucopolysaccharidosis type I after hematopoietic stem cell transplantation: results of an international consensus procedure

Pathogenesis of mitral valve disease in mucopolysaccharidosis VII dogs

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