A5076624766- RNA regulation and disease
- Lysosomal Storage Disorders Research
- Advanced MRI Techniques and Applications
- Cytomegalovirus and herpesvirus research
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- interferon and immune responses
- RNA modifications and cancer
- Atomic and Subatomic Physics Research
- Connexins and lens biology
- Cardiac Imaging and Diagnostics
- Systemic Lupus Erythematosus Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cerebral Palsy and Movement Disorders
- Neurological Disease Mechanisms and Treatments
- Peroxisome Proliferator-Activated Receptors
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Trypanosoma species research and implications
- Folate and B Vitamins Research
- Retinoids in leukemia and cellular processes
- Fetal and Pediatric Neurological Disorders
- Trace Elements in Health
- Cytokine Signaling Pathways and Interactions
Universität Hamburg
2015-2024
University Medical Center Hamburg-Eppendorf
2015-2024
Kinderkrebs-Zentrum Hamburg
2024
Uniwersytecki Szpital Dziecięcy
2024
Children's Clinical University Hospital
2024
Klinik und Poliklinik für Kinder- und Jugendmedizin
2008-2021
Amsterdam UMC Location Vrije Universiteit Amsterdam
2017
Diponegoro University
2017
Eppendorf (Germany)
2013-2015
Massachusetts General Hospital
2011
Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in genes encoding genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder shares features with autoimmune disease systemic lupus erythematosus (SLE). Here we determined heterozygous parents of AGS patients exhibit an intermediate phenotype and demonstrated genetic association between rare RNASEH2 sequence...
In the large group of genetically undetermined infantile-onset mitochondrial encephalopathies, multiple defects DNA-related respiratory-chain complexes constitute a frequent biochemical signature. order to identify responsible genes, we used exome-next-generation sequencing in selected cohort patients with this an isolated patient, found two mutant alleles for EARS2, gene encoding glutamyl–tRNA synthetase. The brain magnetic resonance imaging patient was hallmarked by extensive symmetrical...
G(M2) gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation the brain. Onset during infancy leads to rapid neurodegeneration death before 4 years age. We set out quantify rate functional decline infantile gangliosidosis on basis patient surveys a comprehensive review existing literature.Patients with (N = 237) were surveyed via questionnaire National Tay Sachs & Allied Diseases Association (NTSAD). These data supplemented...
<h3>BACKGROUND AND PURPOSE:</h3> Metachromatic leukodystrophy (MLD) is a devastating demyelinating disease for which novel therapies are being tested. We hypothesized that MR imaging of brain lesion involvement in MLD could be quantified along scale. <h3>MATERIALS METHODS:</h3> Thirty-four images 28 patients with proved biochemical and genetic defects were reviewed: 10 late infantile, 16 juvenile, 2 adult MLD. All reviewed by experienced neuroradiologists neurologists (2 readers Germany, the...
<h3>Importance</h3> Allogeneic hematopoietic stem cell transplantation (HSCT) has been the only treatment option clinically available during last 20 years for juvenile metachromatic leukodystrophy (MLD), reported with variable outcome and without comparison natural course of disease. <h3>Objective</h3> To compare long-term patients who underwent allogeneic HSCT control did not among a cohort MLD. <h3>Design, Setting, Participants</h3> Patients MLD born between 1975 2009 received at median...
IFIH1 gain-of-function has been reported as a cause of type I interferonopathy encompassing spectrum autoinflammatory phenotypes including Aicardi–Goutières syndrome and Singleton Merten syndrome. Ascertaining patients through European North American collaboration, we set out to describe the molecular, clinical interferon status cohort individuals with pathogenic heterozygous mutations in IFIH1. We identified 74 from 51 families segregating total 27 likely Ten adult individuals, 13.5% all...
Pelizaeus–Merzbacher disease (PMD) is an untreatable and fatal leukodystrophy. In a model of PMD with perturbed blood–brain barrier integrity, cholesterol supplementation promotes myelin membrane growth. Here, we show that in contrast to the mouse model, dietary two patients did not lead major advancement hypomyelination, potentially because intact precludes its entry into CNS. We therefore turned preserved integrity high-fat/low-carbohydrate ketogenic diet restored oligodendrocyte increased...
Metachromatic leukodystrophy (MLD) is a rare, genetic neurodegenerative disease. It leads to progressive demyelination resulting in regression of development and early death. With regard experimental therapies, knowledge the natural course disease highly important. We aimed analyse onset character first symptoms MLD provide detailed data concerning language cognition. Patients with were recruited nationwide within scope German research network LEUKONET. 59 patients' questionnaires (23...
To provide an overview of clinical and MRI characteristics the different variants leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) identify possible differentiating features.We performed international multi-institutional, cross-sectional observational study in patients genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians retrospective chart review.We included 204 classic MLC, 187 whom had recessive mutations MLC1 (MLC1...
An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, recent genetic characterization two families a common AIFM1 mutation. In our study, 12 patients (6 families) H-SMD were identified underwent comprehensive assessment accompanied whole-exome sequencing (WES). Pedigree analysis all was consistent recessive inheritance. Presentation typically occurred...
Abstract Context 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, POLR3K. The endocrine growth abnormalities associated with this have not been thoroughly investigated to date. Objective To systematically characterize of patients leukodystrophy. Design An international cross-sectional study was performed on 150...
Abstract Biallelic variants in POLR3A cause 4H leukodystrophy, characterized by hypomyelination combination with cerebellar and pyramidal signs variable non-neurological manifestations. Basal ganglia are spared dystonia is not prominent. Three patients POLR3A, an atypical presentation dystonia, MR involvement of putamen caudate nucleus (striatum) red have previously been reported. Genetic, clinical findings 18 MRI scans from nine homozygous or compound heterozygous predominant striatal...
Abstract Background Canavan disease (CD, MIM # 271900) is a rare and devastating leukodystrophy of early childhood. To identify clinical features that could serve as endpoints for treatment trials, the course CD was studied retrospectively prospectively in 23 patients. Results were compared with data patients reported three prior large series. Kaplan Meier survival analysis including log rank test performed pooled 82 (study cohort literature patients). Onset symptoms between 0 6 months....
Abstract Background Metachromatic Leukodystrophy (MLD) is a rare lysosomal disorder. Patients suffer from relentless neurological deterioration leading to premature death. Recently, new treatment modalities, including gene therapy and enzyme replacement therapy, have been developed. Those advances increase the need for high-quality research infrastructure adequately compare treatments, execute post-marketing surveillance, perform health technology assessments (HTA). To facilitate this, group...
<b><i>Introduction:</i></b> Familial isolated deficiency of vitamin E (VED or AVED; MIM #277460) is a progressive neurodegenerative disorder resembling Friedreich ataxia. It caused by the α-tocopherol transfer protein that prevents patients from retaining E. Oral supplements are an accepted treatment, but detailed dosage recommendations and reports on long-term therapeutic results scarce. <b><i>Methods:</i></b> The first patient with VED was...
Abstract Objective To identify a pharmacological compound targeting macrophages, the most affected immune cells in inflammatory X‐linked adrenoleukodystrophy (cerebral X‐ALD) caused by ABCD1 mutations and involved success of hematopoietic stem cell transplantation gene therapy. Methods A comparative database analysis elucidated epigenetic repressing mechanism related ABCD2 macrophages identified histone deacetylase (HDAC) inhibitor Vorinostat as to induce these compensate for deficiency. In...
<b>Objective</b> This study aims to ascertain frequency of mutations in <i>POLR3A</i> or <i>POLR3B</i>, which are associated with 4H leukodystrophy, a cohort patients unclassified hypomyelination. <b>Methods and Results</b> In 22 the magnetic resonance imaging (MRI) diagnosis hypomyelination without typical clinical signs, we evaluated MRI features. Developmental delay intellectual disability, ataxia, spasticity were frequent symptoms. <i>POLR3B</i> sequenced. A compound heterozygote...
Background: Leukodystrophies are a group of rare genetic diseases that primarily affect the white matter central nervous system. The broad spectrum metabolic and pathological causes leads to manifestations at any age, most often in childhood adolescence, variety symptoms. usually progressive, resulting severe disabilities premature death. Progressive visual impairment is common symptom. Currently, no overview manifold neuro-ophthalmologic impact leukodystrophies exists. Methods: Data from...