78 research outputs found
Limitations of drug registries to evaluate orphan medicinal products for the treatment of lysosomal storage disorders
Low frequency maintenance therapy with imiglucerase in adult type I Gaucher disease: a prospective randomized controlled trial
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Quantification of bone involvement in Gaucher disease: MR imaging bone marrow burden score as an alternative to dixon quantitative chemical shift MR imaging - Initial experience
PURPOSE: To develop a semiquantitative magnetic resonance (MR) imaging bone marrow burden (BMB) score with inclusion of both axial and peripheral bone marrow in Gaucher disease as an alternative to MR imaging with the Dixon quantitative chemical shift imaging (QCSI) technique.MATERIALS AND METHODS: Two experienced musculoskeletal radiologists with no experience in evaluating Gaucher disease blindly analyzed MR images of lumbar spines and femora. Interobserver and intraobserver variability were tested. In addition, the BMB score was determined as a parameter to evaluate bone marrow response to enzyme supplementation therapy. Finally, the BMB score was compared with fat fraction measurements obtained with Dixon QCSI. Differences between groups were analyzed by using the nonparametric Mann-Whitney test. A P value of less than .05 was considered to represent significance. Correlation was calculated by using two-tailed nonparametric rank correlation (Spearman Ï).RESULTS: In 30 patients (mean age, 39.3 years; age range, 12â71 years) the mean fat fraction was 0.20 (range, 0.08â0.40). The BMB score range was 3â13 points. A significant correlation was found between the two observers when using BMB (Ï = 0.91, P P P CONCLUSION: BMB is a reproducible semiquantitative scoring system that is easy to use. It combines MR imaging of both axial and peripheral bone marrow and shows a significant correlation with QCSI.FWN â Publicaties zonder aanstelling Universiteit Leide
Renal involvement in a patient with the chronic visceral subtype of acid sphingomyelinase deficiency resembles Fabry disease
Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease (LSD) in which sphingomyelin accumulates due to deficient acid sphingomyelinase. In the chronic visceral subtype, organ manifestations are generally limited to the spleen, liver, and lungs. We report a male patient with the chronic visceral subtype who developed proteinuria and renal insufficiency at the age of 49. In renal tissue, foam cells were observed in the glomeruli as well as sphingomyelin accumulation within podocytes, mesangial cells, endothelial cells, and tubular epithelial cells. Although macrophages are the primary storage cells in both ASMD and Gaucher disease, comparison to the histopathological findings in Gaucher and Fabry disease revealed a diffuse storage pattern in multiple renal cell types, closer resembling the pattern found in Fabry disease.Medical Biochemistr
Glycoprotein non-metastatic protein B (GPNMB) plasma values in patients with chronic visceral acid sphingomyelinase deficiency
Acid sphingomyelinase deficiency (ASMD) is a rare LSD characterized by lysosomal accumulation of sphingomyelin, primarily in macrophages. With the recent availability of enzyme replacement therapy, the need for biomarkers to assess severity of disease has increased. Glycoprotein non-metastatic protein B (GPNMB) plasma levels were demonstrated to be elevated in Gaucher disease. Given the similarities between Gaucher disease and ASMD, the hypothesis was that GPNMB might be a potential biochemical marker for ASMD as well. Plasma samples of ASMD patients were analyzed and GPNMB plasma levels were compared to those of healthy volunteers. Visceral disease severity was classified as severe when splenic, hepatic and pulmonary manifestations were all present and as mild to moderate if this was not the case. Median GPNMB levels in 67 samples of 19 ASMD patients were 185 ng/ml (range 70-811 ng/ml) and were increased compared to 10 healthy controls (median 36 ng/ml, range 9-175 ng/ml, p < 0.001). Median plasma GPNMB levels of ASMD patients with mild to moderate visceral disease compared to patients with severe visceral disease differed significantly and did not overlap (respectively 109 ng/ml, range 70-304 ng/ml and 325 ng/ml, range 165-811 ng/ml, p < 0.001). Correlations with other biochemical markers of ASMD (i.e. chitotriosidase activity, CCL18 and lysosphingomyelin, respectively R = 0.28, p = 0.270; R = 0.34, p = 0.180; R = 0.39, p = 0.100) and clinical parameters (i.e. spleen volume, liver volume, diffusion capacity and forced vital capacity, respectively R = 0.59, p = 0.061, R = 0.5, p = 0.100, R = 0.065, p = 0.810, R = -0.38, p = 0.160) could not be established within this study. The results of this study suggest that GPNMB might be suitable as a biomarker of visceral disease severity in ASMD. Correlations between GPNMB and biochemical or clinical markers of ASMD and response to therapy have to be studied in a larger cohort.Medical Biochemistr
Influence of sex and phenotype on cardiac outcomes in patients with Fabry disease
Objective: This study describes the influence of sex and disease phenotype on the occurrence of cardiac events in Fabry disease (FD). Methods: Cardiac events from birth to last visit (median age 50 years) were recorded for 213 patients with FD. Patients were categorised as follows: men with classical FD (n=57), men with non-classical FD (n=26), women with classical FD (n=98) and women with non-classical FD (n=32), based on the presence of classical FD symptoms, family history (men and women), biomarkers and residual enzyme activity (men). Event rates per 1000 patient-years after the age of 15 years and median event-free survival (EVS) age were presented. Influence of disease phenotype, sex and their interaction was studied using Firth's penalised Cox regression. Results: The event rates of major cardiovascular events (combined endpoint cardiovascular death (CVD), heart failure (HF) hospitalisation, sustained ventricular arrhythmias (SVAs) and myocardial infarction) were 11.0 (95% CI 6.6 to 17.3) in men with classical FD (EVS 55 years), 4.4 (95% CI 2.5 to 7.1) in w
Classical galactosemia: neuropsychological and psychosocial functioning beyond intellectual abilities
BACKGROUND: Despite early diagnosis and treatment, Classical Galactosemia (CG) patients frequently develop long-term complications, such as cognitive impairment. Available literature primarily reports on general intellectual abilities and shows a substantially lower Full Scale Intelligence Quotient (FSIQ) in CG patients than in the general population. Both problems in social functioning as well as internalizing problems are often reported in CG patients. The combination of intelligence, cognitive functioning, beh
Plasma globotriaosylsphingosine: diagnostic value and relation to clinical manifestations of Fabry disease
FWN â Publicaties zonder aanstelling Universiteit Leide
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