Hypertrophic cardiomyopathy in mucopolysaccharidoses: Regression after bone marrow transplantation

Viñallonga, Xavier; Sanz, Núria; Balaguer, Albert; Miro, L.; Ortega, Juan José López; Casaldáliga, Jaume

doi:10.1007/bf00798216

Cited by 37 publications

(26 citation statements)

References 5 publications

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“…13 More than 270 human patients with MPS have had results of cardiovascular system evaluations published. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Of these patients, the majority did not have a specific enzyme diagnosis. However, the largest group with an identified diagnosis was MPS I (Hurler syndrome, alphal-iduronidase deficiency).…”

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

“…36,39,[41][42][43][44][45][46] In a 9.5-year-old MPS I child, the ventricular septal thickness and sigmoidal valve thickening were reduced. 36 In another study, a series of 16 children from 3 to 108 months of age with MPS were followed post BMT. 39 Of the 13 MPS I, one MPS IV (Morquio syndrome), and two MPS VI (Maroteaux-Lamy syndrome) patients examined after BMT, two of four cleared a restrictive left ventricle, one of two resolved left ventricular hypertrophy, and there was no change seen in the mitral valve dysplasia or aortic stenosis, each seen in two patients.…”

Section: Figurementioning

confidence: 99%

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Effects of bone marrow transplantation on the cardiovascular abnormalities in canine mucopolysaccharidosis VII

Sammarco

Weil

Just

et al. 2000

Bone Marrow Transplant

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Summary:The genetic mucopolysaccharidoses (MPS) are a family of lysosomal storage diseases resulting from defective catabolism of glycosaminoglycans (GAGs). Echocardiographic abnormalities in dogs with MPS type VII (Sly syndrome, ␤-glucuronidase deficiency) included mitral valve thickening and insufficiency, large aortic dimensions in both the long and short axes, and thickened aortic valves. Grossly, at post mortem examination, there was nodular thickening of the mitral valve, a prominent ductus diverticulum, and a dilated aorta with thickened walls. Histologically, cytoplasmic vacuolation was seen in cells of the mitral valves, coronary arteries, and aorta. By electron microscopy, the cells of the mitral valve were packed with electron-lucent cytoplasmic vacuoles. The mean residual activity of ␤-glucuronidase in the aorta and myocardium was Ͻ1% of normal, the mean hexosaminidase A activity Ͼ2.5 times normal, and the mean GAG concentrations more than twice normal. In three MPS VII dogs that received heterologous BMT at 6 weeks of age, the echocardiographic abnormalities were improved, and the histopathologic and ultrastructural pathology was reduced. In the aorta and myocardium, the mean ␤-glucuronidase activity of the BMT group was 4.5% and 11% of normal, respectively, and the hexosaminidase A activity and GAG concentrations were normalized. Bone Marrow Transplantation (2000) 25, 1289-1297.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Effects of bone marrow transplantation on the cardiovascular abnormalities in canine mucopolysaccharidosis VII

Sammarco

Weil

Just

et al. 2000

Bone Marrow Transplant

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“…1 Hurler's syndrome (HS) is the most severe phenotype, with symptoms appearing shortly after birth, characterized by upper airway obstruction and recurrent chest infections, hepatosplenomegaly, corneal clouding, cardiac dysfunction, skeletal abnormalities, progressive deterioration of the central nervous system and death in early childhood. [1][2][3][4][5][6][7] Hematopoietic stem cell transplantation (SCT) can prevent the progression of HS and provides maximal benefit when performed early in life. 6,8 Enzyme replacement therapy (ERT; Aldurazyme) became recently available for the treatment of MPS-1.…”

Section: Introductionmentioning

confidence: 99%

“…Hydrocephalus is either prevented or stabilized and hearing impairment improves in many children. [9][10][11][12][13] Additionally, successful SCT averts death from cardiac dysfunction 2,5 improves growth and psychomotor development, and prolongs survival. 4,6,7,11,12,14 Significant and often progressive orthopedic anomalies persist however, despite successful SCT, often needing additional interventions.…”

Section: Introductionmentioning

confidence: 99%

Outcomes of hematopoietic stem cell transplantation for Hurler's syndrome in Europe: a risk factor analysis for graft failure

Boelens

Wynn

O’Meara

et al. 2007

Bone Marrow Transplant

196

186

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Hurler's syndrome (HS), the most severe form of mucopolysaccharidosis type-I, causes progressive deterioration of the central nervous system and death in childhood. Allogeneic stem cell transplantation (SCT) before the age of 2 years halts disease progression. Graft failure limits the success of SCT. We analyzed data on HS patients transplanted in Europe to identify the risk factors for graft failure. We compared outcomes in 146 HS patients transplanted with various conditioning regimens and grafts. Patients were transplanted between 1994 and 2004 and registered to the European Blood and Marrow Transplantation database. Risk factor analysis was performed using logistic regression. 'Survival' and 'alive and engrafted'-rate after first SCT was 85 and 56%, respectively. In multivariable analysis, T-cell depletion (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04-0.71; P ¼ 0.02) and reduced-intensity conditioning (OR 0.08; 95% CI 0.02-0.39; P ¼ 0.002) were the risk factors for graft failure. Busulfan targeting protected against graft failure (OR 5.76; 95% CI 1.20-27.54; P ¼ 0.028). No difference was noted between cell sources used (bone marrow, peripheral blood stem cells or cord blood (CB)); however, significantly more patients who received CB transplants had full-donor chimerism (OR 9.31; 95% CI 1.06-82.03; P ¼ 0.044). These outcomes may impact the safety/efficacy of SCT for 'inborn-errors of metabolism' at large. CB increased the likelihood of sustained engraftment associated with normal enzyme levels and could therefore be considered as a preferential cell source in SCT for 'inborn errors of metabolism'.

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Myocardial storage of chondroitin sulfate-containing moieties in Costello syndrome patients with severe hypertrophic cardiomyopathy

et al. 2005

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Costello syndrome is a distinctive multiple congenital anomaly syndrome, characterized by loose soft skin with deep palmar and plantar creases, loose joints, distinctive coarse facial features, skeletal abnormalities, cardiac abnormalities (cardiovascular malformation (CVM), hypertrophic cardiomyopathy, tachycardia), predisposition to malignancy, developmental delays, and mental retardation. Previous studies with cultured fibroblasts from individuals with Costello syndrome demonstrate excessive accumulation of chondroitin sulfate-bearing proteoglycans, associated with both impaired formation of elastic fibers and an unusually high rate of cellular proliferation. Despite multiple clinical reports of cardiac abnormalities, there has been only one previously published report describing post-mortem findings in hearts from Costello syndrome patients. Here we provide a detailed description of the post-mortem findings of the hearts of three children with Costello syndrome. Routine histological examination and results of targeted histochemical and immunohistochemical studies revealed that in addition to cardiomyocyte hypertrophy, these hearts also demonstrated massive pericellular and intracellular accumulation of chondroitin sulfate-bearing proteoglycans and a marked reduction of elastic fibers. Normal stroma was replaced by multifocal collagenous fibrosis. Most peculiar was the finding that the bulk of the chondroitin sulfate accumulated in these Costello syndrome hearts is a chondroitin-6-sulfate. In contrast, deposition of chondroitin-4 sulfate was below the level detected in normal hearts. We propose that an imbalance in sulfation of chondroitin sulfate molecules and subsequent accumulation of chondroitin-6-sulfate in cardiomyocytes contribute to the development of the hypertrophic cardiomyopathy of Costello syndrome.

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Hypertrophic cardiomyopathy in mucopolysaccharidoses: Regression after bone marrow transplantation

Cited by 37 publications

References 5 publications

Effects of bone marrow transplantation on the cardiovascular abnormalities in canine mucopolysaccharidosis VII

Effects of bone marrow transplantation on the cardiovascular abnormalities in canine mucopolysaccharidosis VII

Outcomes of hematopoietic stem cell transplantation for Hurler's syndrome in Europe: a risk factor analysis for graft failure

Myocardial storage of chondroitin sulfate-containing moieties in Costello syndrome patients with severe hypertrophic cardiomyopathy

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