A5044968268- Metabolism and Genetic Disorders
- Muscle metabolism and nutrition
- Amino Acid Enzymes and Metabolism
- Biochemical and Molecular Research
- Diet and metabolism studies
- Folate and B Vitamins Research
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- RNA modifications and cancer
- Glycogen Storage Diseases and Myoclonus
- Metabolomics and Mass Spectrometry Studies
- Biomedical Research and Pathophysiology
- Neonatal Health and Biochemistry
- Genetics and Neurodevelopmental Disorders
- Methemoglobinemia and Tumor Lysis Syndrome
- Neuroscience and Neuropharmacology Research
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Advanced MRI Techniques and Applications
- Genomics and Rare Diseases
- Peroxisome Proliferator-Activated Receptors
- Attention Deficit Hyperactivity Disorder
- Genetic Neurodegenerative Diseases
University of Amsterdam
2002-2025
Emma Kinderziekenhuis
2016-2024
Amsterdam Neuroscience
2014-2024
Amsterdam University Medical Centers
2006-2024
Vrije Universiteit Amsterdam
2003-2022
Amsterdam UMC Location Vrije Universiteit Amsterdam
2011-2020
Boston Children's Hospital
2015-2020
Washington State University Spokane
2015-2020
Harvard University
2020
The University of Sydney
2019
<h3>Objectives:</h3> The study was focused on leukoencephalopathies of unknown cause in order to define a novel, homogeneous phenotype suggestive common genetic defect, based clinical and MRI findings, identify the causal defect shared by patients with this phenotype. <h3>Methods:</h3> Independent next-generation exome-sequencing studies were performed 2 unrelated leukoencephalopathy. findings these compared available MRIs database unclassified leukoencephalopathies; 11 similar abnormalities...
Abstract Alexander disease is a progressive, usually fatal neurological disorder defined by the widespread and abundant presence in astrocytes of protein aggregates called Rosenthal fibers. The most often occurs infants younger than 2 years has been labeled leukodystrophy because an accompanying severe myelin deficit frontal lobes. Later onset forms have also recognized based on In these cases, clinical signs pathology can be quite different from infantile form, raising question whether they...
Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase-1 and -2 (IDH1 IDH2) were recently discovered human neoplastic disorders. These disable enzymes' normal ability to convert 2-ketoglutarate (2-KG) confer on enzymes a new function: 2-KG d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline IDH2 that alter enzyme residue Arg(140) 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), rare neurometabolic disorder characterized by...
Abstract Objective Folinic acid–responsive seizures and pyridoxine‐dependent epilepsy are two treatable causes of neonatal epileptic encephalopathy. The former is diagnosed by characteristic peaks on cerebrospinal fluid (CSF) monoamine metabolite analysis; its genetic basis has remained elusive. latter due to α‐aminoadipic semialdehyde (α‐AASA) dehydrogenase deficiency, associated with pathogenic mutations in the ALDH7A1 ( antiquitin ) gene. We report patients whose CSF showed marker folinic...
<h3>Background</h3> Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview phenotype, genotype and phenotype–genotype correlation has lacking. <h3>Methods</h3> We performed retrospective study clinical, biochemical molecular genetic data 101 males with creatine from 85 families pathogenic mutation the gene (<i>SLC6A8</i>). <h3>Results conclusions</h3> Most patients...
Abstract Objective: A high percentage of grade II and III gliomas have mutations in the gene encoding isocitrate dehydrogenase ( IDH1 ). This mutation is always a heterozygous point that affects amino acid arginine at position 132 results loss its native enzymatic activity gain alternative (producing D‐2‐hydroxyglutarate). The objective this study was to investigate cellular effects R132H . Methods: Functional consequences were examined among others using fluorescence‐activated cell sorting,...
Guanidinoactetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine synthesis. The authors analyzed clinical, biochemical, and molecular findings in 27 patients.The collected data from questionnaires literature reports. A score including degree intellectual disability, epileptic seizures, movement was developed used to classify clinical phenotype as severe, moderate, or mild. Score biochemical were assessed before during treatment with oral substitution alone...
Alexander disease is most commonly associated with macrocephaly and, on MRI, a leukoencephalopathy frontal preponderance. The caused by mutation of the GFAP gene. Clinical and MRI phenotypic variation have been increasingly recognized.The authors studied seven patients disease, diagnosed based mutations in gene, who presented unusual findings. reviewed clinical history, abnormalities, mutations.All had juvenile onset signs brainstem or spinal cord dysfunction. None macrocephaly....
Succinate semialdehyde dehydrogenase (SSADH; ALDH5A1) deficiency, a rare metabolic disorder that disrupts the normal degradation of GABA, gives rise to highly heterogeneous neurological phenotype ranging from mild very severe. The nature mutation has so far been reported in patients six families world wide and eight different mutations were described. Here we report mutational spectrum 48 additional unrelated geographic origin. We detected 27 novel at cDNA level, which 26 could be attributed...
Abstract The purpose of this study was to describe unusual variants Alexander's disease. We studied 10 patients who did not meet previously established magnetic resonance imaging (MRI) criteria for disease, but whom diagnosis considered because Rosenthal fibers at histological examination or presence some MRI features suggestive Sequence analysis the GFAP gene performed. In eight patients, results showed predominantly posterior fossa lesions, especially multiple tumor‐like brainstem lesions....