A5025385826- Lysosomal Storage Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Carbohydrate Chemistry and Synthesis
- Trypanosoma species research and implications
- Child Nutrition and Feeding Issues
- Cellular transport and secretion
- Metabolism and Genetic Disorders
- Biochemical and Molecular Research
- Glycosylation and Glycoproteins Research
- Genetics and Neurodevelopmental Disorders
- Biomedical Research and Pathophysiology
- Genomics and Rare Diseases
- Digestive system and related health
- Diet and metabolism studies
- Neonatal Health and Biochemistry
- Calcium signaling and nucleotide metabolism
- Blood disorders and treatments
- Oral and gingival health research
- Porphyrin Metabolism and Disorders
- Pancreatic function and diabetes
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- CRISPR and Genetic Engineering
- Renal Diseases and Glomerulopathies
- Amino Acid Enzymes and Metabolism
- Neurogenetic and Muscular Disorders Research
Erasmus MC
2011-2022
Erasmus University Rotterdam
2004-2013
Erasmus MC - Sophia Children’s Hospital
1995-2008
Maastricht University
2006
University Medical Center Utrecht
1999
Institute of Child Health
1997
Ajuntament de Barcelona
1996
Duke University Hospital
1993
Duke Medical Center
1993
Commonwealth Scientific and Industrial Research Organisation
1993
In normal human fibroblasts, an enzymically active 85,000-dalton precursor form of beta-galactosidase is processed, via a number intermediates, into mature 64,000-dalton form. addition there inactive 32,000-dalton component and its 54,000-dalton precursor. fibroblasts from patients with combined deficiency neuraminidase these last two components are absent hardly any can be demonstrated. Nevertheless, in the mutant synthesized processed normally. The excessive intralysosomal degradation that...
Objective. Recent reports warn that the worldwide cell culture capacity is insufficient to fulfill increasing demand for human protein drugs. Production in milk of transgenic animals an attractive alternative. Kilogram quantities product per year can be obtained at relatively low costs, even small such as rabbits. We tested long-term safety and efficacy recombinant α-glucosidase (rhAGLU) from rabbit treatment lysosomal storage disorder Pompe disease. The disease occurs with estimated...
Abstract Pompe's disease is an autosomal recessive myopathy. The characteristic lysosomal storage of glycogen caused by acid α‐glucosidase deficiency. Patients with late‐onset present progressive muscle weakness also affecting pulmonary function. In search a treatment, we investigated the feasibility enzyme replacement therapy recombinant human from rabbit milk. Three patients (aged 11, 16, and 32 years) were enrolled in study. They all wheelchair‐bound two them ventilator dependent history...
Information about 255 children and adults with Pompe disease was gathered through a questionnaire. Disease severity associated duration not age; an early manifestation of the implied earlier wheelchair or ventilator dependency. The patient group under age 15 included subgroup more severe rapid course disease. They require intensive follow-up intervention, before irreversible damage has occurred.
Pompe disease was named after the Dutch pathologist Dr JC who reported about a deceased infant with idiopathic hypertrophy of heart. The clinical findings were failure to thrive, generalized muscle weakness and cardio-respiratory failure. key pathologic finding massive storage glycogen in heart, skeletal many other tissues. classified as type II decades later shown be lysosomal disorder caused by acid α-glucosidase deficiency. spectrum appeared much broader than originally recognized. Adults...
Due partly to physicians' unawareness, many adults with Pompe disease are diagnosed great delay. Besides, it is not well known which factors influence the rate of progression, and thus outcome. We delineated specific clinical features in adults, mapped out distribution severity muscle weakness, sequence involvement individual groups. Furthermore, we defined natural course identified prognostic for progression. conducted a single-center, prospective, observational study. Muscle strength...
Abstract Background Pompe disease is a rare metabolic myopathy for which disease-specific enzyme replacement therapy (ERT) has been available since 2006. ERT shown efficacy concerning muscle strength and pulmonary function in adult patients. However, no data on the effect of survival patients are currently available. The aim this study was to assess with disease. Methods Data were collected as part an international observational conducted between 2002 2011, followed annual basis....
The synthesis and posttranslational modification of lysosomal acid alpha-glucosidase were studied in a cell-free translation system mammalian cells transfected with cDNA constructs. newly synthesized precursor, sequestered the endoplasmic reticulum, was demonstrated to be membrane-bound by lack signal peptide cleavage, catalytically inactive. Sugar chain shown occur Golgi complex dependent on rate transport. From trans-Golgi network different routes found followed alpha-glucosidase. A...
The substrate analogue conduritol B epoxide (CBE) is demonstrated to be an active site-directed inhibitor of human lysosomal alpha-glucosidase. A competitive mode inhibition obtained with glycogen as natural and 4-methylumbelliferyl-alpha-D-glucopyranoside artificial substrate. inactivation the enzyme time concentration dependent results in covalent binding CBE. Catalytic activity required for occur. CBE-labeled peptides containing catalytic residue alpha-glucosidase were isolated identified...
Patients with glycogen storage disease type II (GSDII, Pompe disease) suffer from progressive muscle weakness due to acid α-glucosidase deficiency. The is inherited as an autosomal recessive trait a spectrum of clinical phenotypes. We have investigated 29 cases GSDII and thereby identified 55 pathogenic mutations the gene (GAA) encoding maltase. There were 34 different identified, 22 which novel. All missense two other unpredictable effect on synthesis function transiently expressed in COS...
The gene coding for human lysosomal alpha-glucosidase was cloned and its structure determined. is approx. 20 kb long, contains exons. first exon non-coding. sequence of the putative catalytic site domain interrupted in middle by an intron 101 bp. This not conserved highly similar region rabbit isomaltase genes. promoter defined a CAT assay start mRNA determined primer extension. has features characteristic ‘housekeeping’ gene. GC content high (80%) distinct TATA CCAAT motifs are lacking. Two...
Glycogenosis type II is an inherited lysosomal storage disease with acid alpha-glucosidase deficiency as the primary defect. Using cultured skin fibroblasts, we have studied biosynthesis of in clinically different forms this disease. Three unrelated patients were identified (one infantile, one a juvenile, and adult form disease) producing normal quantities 110-kDa precursor alpha-glucosidase. However, post-translational modification to mature 76-kDa enzyme protein was either completely...
Pompe disease is a rare lysosomal storage disorder characterized by muscle weakness and wasting. The majority of adult patients have slowly progressive disease, which gradually impairs mobility respiratory function may lead to wheelchair ventilator dependency. It as yet unknown what extent the reduces life span these patients. Our objective was determine survival adults with not receiving ERT identify prognostic factors associated survival.Data 268 were collected in prospective international...