Usefulness of bone marrow transplantation in the Hurler syndrome

Braunlin, Elizabeth; Stauffer, Nanci; Peters, Charles; Bass, John L.; Berry, James M.; Hopwood, John J.; Krivit, William

doi:10.1016/s0002-9149(03)00909-3

Cited by 96 publications

(68 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, aortic insufficiency developed de novo or worsened in 89% of patients at 12 years after performing hematopoietic stem cell transplantation at ~2 years [30] and in 60% of patients at 4-6 years after starting enzyme replacement therapy [31,32]. Although pathological data were not available, progressive fragmentation of the elastic fibers likely contributed to worsening aortic valve function.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

Tittiger

Knutsen

et al. 2008

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

Mucopolysaccharidosis I (MPS I), known as Hurler syndrome in the severe form, is a lysosomal storage disease due to -L-iduronidase (IDUA) deficiency. It results in fragmentation of elastin fibers in the aorta and heart valves via mechanisms that are unclear, but may result from the accumulation of the glycosaminoglycans heparan and dermatan sulfate. Elastin fragmentation causes aortic dilatation and valvular insufficiency, which can result in cardiovascular disease. The pathophysiology of aortic disease was evaluated in MPS I mice. MPS I mice have normal elastic fiber structure and aortic compliance at early ages, which suggests that elastin assembly is normal. Elastin fragmentation and aortic dilatation are severe at 6 months, which is temporally associated with marked increases in mRNA and enzyme activity for two elastin-degrading proteins, matrix metalloproteinase-12 (MMP-12) and cathepsin S. Upregulation of these genes likely involves activation of STAT proteins, which may be induced by structural stress to smooth muscle cells from accumulation of glycosaminoglycans in lysosomes. Neonatal intravenous injection of a retroviral vector normalized MMP-12 and cathepsin S mRNA levels and prevented aortic disease. We conclude that aortic dilatation in MPS I mice is likely due to degradation of elastin by MMP-12 and/or cathepsin S. This aspect of disease might be ameliorated by inhibition of the signal transduction pathways that upregulate expression of elastase proteins, or by inhibition of elastase activity. This could result in a treatment for patients with MPS I, and might reduce aortic aneurism formation in other disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

Tittiger

Knutsen

et al. 2008

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

show abstract

“…In these patients, allogeneic HSCT stabilises cognitive skills, normalises liver and spleen volume, improves survival 17, reduces ventricular hypertrophy and maintains cardiac function 18. Individual patients with an intermediate phenotype may also be considered for HSCT if the benefits outweigh the risks and an optimal donor is available 16.…”

Section: Introductionmentioning

confidence: 99%

Easy‐to‐use algorithm would provide faster diagnoses for mucopolysaccharidosis type I and enable patients to receive earlier treatment

Tylki‐Szymańska

Meırleır²,

Rocco

et al. 2018

Acta Paediatrica

View full text Add to dashboard Cite

AimThe aim of this study was to develop an algorithm to prompt early clinical suspicion of mucopolysaccharidosis type I (MPS I).MethodsAn international working group was established in 2016 that comprised 11 experts in paediatrics, rare diseases and inherited metabolic diseases. They reviewed real‐world clinical cases, selected key signs or symptoms based on their prevalence and specificity and reached consensus about the algorithm. The algorithm was retrospectively tested.ResultsAn algorithm was developed. In patients under two years of age, kyphosis or gibbus deformity were the key symptoms that raised clinical suspicion of MPS I and in those over two years they were kyphosis or gibbus deformity, or joint stiffness or contractures without inflammation. The algorithm was tested on 35 cases, comprising 16 Hurler, 10 Hurler–Scheie, and nine Scheie patients. Of these 35 cases, 32 (91%) – 16 Hurler, nine Hurler–Scheie and seven Scheie patients – would have been referred earlier if the algorithm had been used.ConclusionThe expert panel developed and tested an algorithm that helps raise clinical suspicion of MPS I and would lead to a more prompt final diagnosis and allow earlier treatment.

show abstract

“…2 Enzyme delivery by engrafted donor cells ameliorates the course of the disease and improves overall survival. Besides the beneficial effects on visceral features, such as hepatosplenomegaly, cardiac disease, coarse facial features and upper airway obstruction, [3][4][5] preservation of neuropsychological function may be achieved in children who have minimal or no central nervous system disease at the time of transplant. 4,[6][7][8] Nevertheless, some symptoms, such as the skeletal abnormalities, may progress after successful HCT.…”

Section: Introductionmentioning

confidence: 99%

Haematopoietic cell transplantation (HCT) in combination with enzyme replacement therapy (ERT) in patients with Hurler syndrome

Cox-Brinkman

Boelens

et al. 2006

Bone Marrow Transplant

View full text Add to dashboard Cite

Hurler syndrome (MPS 1H) is the severe form of mucopolysaccharidosis type 1 (MPS 1). Haematopoietic cell transplantation (HCT) is the treatment of choice, but carries a high incidence of graft failure and morbidity. The use of enzyme replacement therapy (ERT) might improve the clinical signs and symptoms before HCT, resulting in less transplantation-related complications. Moreover, clearance of glycosaminoglycans (GAG's) from the bone marrow might improve engraftment. Twenty-two patients with MPS 1H received one or more HCT procedures in combination with ERT. One patient with severe cardiomyopathy improved significantly after ERT. All children were in a relatively good clinical condition before HCT. Of patients 59, 82 and 86% were alive and engrafted after one, two and three HCT procedures, respectively. Two patients died after repetitive HCT. No serious ERTinfusion-related toxicity occurred. ERT with HCT was well tolerated. Neither a positive nor a negative effect on the number of patients who are alive and engrafted after receiving ERT before HCT as compared to a historic cohort was noted. However, patients in a poor clinical condition before HCT might benefit from ERT.

show abstract

Usefulness of bone marrow transplantation in the Hurler syndrome

Cited by 96 publications

References 11 publications

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

Easy‐to‐use algorithm would provide faster diagnoses for mucopolysaccharidosis type I and enable patients to receive earlier treatment

Haematopoietic cell transplantation (HCT) in combination with enzyme replacement therapy (ERT) in patients with Hurler syndrome

Contact Info

Product

Resources

About