A5004682617- Folate and B Vitamins Research
- Genetics and Neurodevelopmental Disorders
- Metabolism and Genetic Disorders
- Neurogenetic and Muscular Disorders Research
- Neonatal and fetal brain pathology
- Autism Spectrum Disorder Research
- Biotin and Related Studies
- RNA regulation and disease
- Myasthenia Gravis and Thymoma
- Neonatal Respiratory Health Research
- Fetal and Pediatric Neurological Disorders
- Traumatic Brain Injury and Neurovascular Disturbances
- Click Chemistry and Applications
- Child Nutrition and Feeding Issues
- Muscle activation and electromyography studies
- RNA Research and Splicing
- Genetic Neurodegenerative Diseases
- Selenium in Biological Systems
- Ion Transport and Channel Regulation
- Pharmacological Effects and Toxicity Studies
- Herpesvirus Infections and Treatments
- Trace Elements in Health
- Psychoanalysis and Psychopathology Research
- Glycogen Storage Diseases and Myoclonus
- Lysosomal Storage Disorders Research
University of Liège
2002-2022
Centre Hospitalier Universitaire de Liège
2009-2019
Universitätsklinikum Aachen
1996-2009
Centre for Biomedical Network Research on Rare Diseases
2008
Instituto de Salud Carlos III
2008
Hospital Sant Joan de Déu Barcelona
2008
FH Aachen
2008
RWTH Aachen University
1993-2007
Baylor College of Medicine
2005
Baylor University Medical Center
2005
We describe members of 4 kindreds with a previously unrecognized syndrome characterized by seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (hypokalemia, metabolic alkalosis, hypomagnesemia). By analysis linkage we localize the putative causative gene to 2.5-Mb segment chromosome 1q23.2-23.3. Direct DNA sequencing KCNJ10, which encodes an inwardly rectifying K(+) channel, identifies unidentified missense or nonsense mutations on both alleles in all...
In infantile-onset cerebral folate deficiency, 5-methyltetrahydrofolate (5MTHF) levels in the cerebrospinal fluid are low, but serum and erythrocytes normal. We examined specimens from 28 children with 5 of their mothers, age-matched control subjects, 41 patients an unrelated neurologic disorder. Serum 25 0 subjects contained high-affinity blocking autoantibodies against membrane-bound receptors that present on choroid plexus. Oral folinic acid normalized 5MTHF led to clinical improvement....
Cerebral folate deficiency (CFD) can be defined as any neurological syndrome associated with low cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF), the active metabolite, in presence of normal metabolism outside nervous system. CFD could result from either disturbed transport or increased turnover within central system (CNS). We report on a novel neurometabolic 20 children, which we term 'idiopathic CFD'. Typical features became manifest age 4 months, starting marked unrest,...
Reduced folate transport to the CNS was identified in two autism spectrum disorders, i.e., Rett syndrome and infantile low-functioning with neurological abnormalities. Twenty-five patients early-onset or without deficits, were evaluated for serum folate, cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF), FR autoantibodies of blocking type determine significance receptor (FR) respect across blood-CSF barrier. In spite normal CSF 5MTHF low 23 25 patients. The reduced 19 these could be...
Two children with severe neurodevelopmental retardation and elevated liver function tests developed intractable seizures during the first year of life. Detectable neurometabolic conditions have been ruled out. At time evidence for systemic selenium deficiency could be documented. The youngest patient, who manifested fits from fourth day life, died at age ten months. Neuropathologic examination was consistent Progressive Neuronal Degeneration Childhood (PNDC) disease or formerly known as...
The authors describe a 6-year-old girl with developmental delay, psychomotor regression, seizures, mental retardation, and autistic features associated low CSF levels of 5-methyltetrahydrofolate, the biologically active form folates in blood. Folate B12 were normal peripheral tissues, suggesting cerebral folate deficiency. Treatment folinic acid corrected abnormalities improved motor skills.
Patients with autism spectrum disorder (ASD) may have low brain serotonin concentrations as reflected by the end-metabolite 5-hydroxyindolacetic acid (5HIAA) in cerebrospinal fluid (CSF).We sequenced candidate genes SLC6A4 (SERT), SLC29A4 (PMAT), and GCHFR (GFRP), followed whole exome analysis.The known heterozygous p.Gly56Ala mutation gene was equally found ASD control populations. Using a genetic approach, we identified, 8 patients of cohort 248 ASD, high prevalence (3.2%) three novel...
TRPM3 is a temperature- and neurosteroid-sensitive plasma membrane cation channel expressed in variety of neuronal non-neuronal cells. Recently, rare de novo variants were identified individuals with developmental epileptic encephalopathy, but the link between activity disease remains poorly understood. We previously reported that two disease-associated lead to gain function . Here, we report further 10 patients carrying one seven additional heterozygous missense variants. These present...
<b><i>Objective:</i></b> To describe three unrelated children with a distinctive variant of Aicardi-Goutières syndrome (AGS) characterized by microcephaly, severe mental and motor retardation, dyskinesia or spasticity, occasional seizures. <b><i>Results:</i></b> Neuroimaging showed bilateral calcification basal ganglia white matter. CSF glucose, protein, cell count, interferon alpha were normal. Abnormal findings included extremely high neopterin (293 to 814 nmol/L; normal 12 30 nmol/L)...
<b><i>Objective:</i></b> Mutation analysis of the acetylcholine receptor (AChR) ε subunit gene in patients with sporadic or autosomal recessive congenital myasthenic syndromes (CMS). <b><i>Background:</i></b> The nicotinic AChR skeletal muscle is a neurotransmitter-gated ion channel that mediates synaptic transmission at vertebrate neuromuscular junction. Mutations its may cause syndromes. A recently described mutation exon 12 (ε1267delG) disrupts cytoplasmic loop and fourth transmembrane...
In cerebral folate deficiency syndrome, the presence of autoantibodies against receptor (FR) explains decreased transport to central nervous system and clinical response folinic acid. Autoantibody crossreactivity with milk FR from different species prompted us test effect a milk‐free diet. Intervention milkfree diet in 12 children (nine males, three females; mean age 6y [SD 4y 11mo], range 1‐19y), autoantibody titer significantly 2.08pmol blocked per ml serum (SD 2.1; 0.24‐8.35) 0.35pmol...
Cerebral folate deficiency (CFD) has been defined as any neuropsychiatric condition associated with isolated lowering of 5-methyltetrahydrofolate (5-MTHF) levels in CSF and normal systemic metabolism.1 CFD detected the infantile-onset CFD syndrome (mediated by serum receptor [FR] autoantibodies blocking type1) Aicardi-Goutieres Rett syndromes. In Kearns-Sayre (KSS), or low 5-MTHF have long recognized.2,3 Because active transport across choroid plexus epithelial cells is mediated...
<b><i>Background:</i></b> Previous CSF studies in Rett syndrome suggest reduced turnover of the biogenic monoamines serotonin and dopamine. Because diminished may result from CNS folate depletion, authors studied transport across blood–brain barrier. <b><i>Methods:</i></b> In four patients with syndrome, measured values 5-methyltetrahydrofolate (5MTHF), monoamine end-metabolites, pterins together serum red blood cell folate. CSF, overall binding capacity by two soluble folate-binding...
Normal brain development and function depend on the active transport of folates across blood-brain barrier. The folate receptor-1 (FR 1) protein is localized at basolateral surface choroid plexus, which characterized by a high binding affinity for circulating 5-methyltetrahydrofolate (5-MTHF).