References of "RAMAEKERS, Vincent"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailDissection artérielle cérébrale chez l'enfant
BARREA, Christophe ULg; RAMAEKERS, Vincent ULg; OTTO, Bernard ULg et al

Conference (2014, March)

Detailed reference viewed: 28 (3 ULg)
Full Text
Peer Reviewed
See detailThe diagnostic utility of folate receptor autoantibodies in blood
Sequeira, JM; RAMAEKERS, Vincent ULg; Quadros, EV

in Clinical Chemistry & Laboratory Medicine (2013), 51(3), 545-54

Detailed reference viewed: 19 (5 ULg)
Full Text
Peer Reviewed
See detailRole of folate receptor autoantibodies in infantile autism
RAMAEKERS, Vincent ULg; Quadros, E. V.; Sequeira, J. M.

in Molecular Psychiatry (2013), 18(3), 270-1

Detailed reference viewed: 21 (2 ULg)
Full Text
Peer Reviewed
See detailClinical recognition and aspects of the cerebral folate deficiency syndromes
RAMAEKERS, Vincent ULg; Sequeira, JM; Quadros, EV

in Clinical Chemistry & Laboratory Medicine (2013), 51(3), 497-511

Detailed reference viewed: 29 (2 ULg)
Full Text
Peer Reviewed
See detailClinical utility gene card for: Biotinidase deficiency
Küry, S.; RAMAEKERS, Vincent ULg; Bézieau, S. et al

in European Journal of Human Genetics (2012), 20(5), 592

Detailed reference viewed: 10 (0 ULg)
Full Text
Peer Reviewed
See detailAutism associated with low 5-hydroxyindolacetic acid in CSF and the heterozygous SLC6A4 gene Gly56Ala plus 5-HTTLPR L/L promoter variants.
Adamsen, Dea; Meili, David; Blau, Nenad et al

in Molecular Genetics & Metabolism (2011), 102(3), 368-73

The known Gly56Ala mutation in the serotonin transporter SERT (or 5-HTT), encoded by the SLC6A4 gene, causes increased serotonin reuptake and has been associated with autism and rigid-compulsive behavior ... [more ▼]

The known Gly56Ala mutation in the serotonin transporter SERT (or 5-HTT), encoded by the SLC6A4 gene, causes increased serotonin reuptake and has been associated with autism and rigid-compulsive behavior. We report a patient with macrocephaly from birth, followed by hypotonia, developmental delay, ataxia and a diagnosis of atypical autism (PDD-NOS) in retrospect at the age of 4(1/2)years. Low levels of the serotonin end-metabolite 5-hydroxyindolacetic acid (5HIAA) in CSF were detected, and SLC6A4 gene analysis revealed the heterozygous Gly56Ala alteration and the homozygous 5-HTTLPR L/L promoter variant. These changes are reported to be responsible for elevated SERT activity and expression, suggesting that these alterations were responsible in our patient for low serotonin turnover in the central nervous system (CNS). Daily treatment with 5-hydroxytryptophan (and carbidopa) led to clinical improvement and normalization of 5HIAA, implying that brain serotonin turnover normalized. We speculate that the mutated 56Ala SERT transporter with elevated expression and basal activity for serotonin re-uptake is accompanied with serotonin accumulation within pre-synaptic axons and their vesicles in the CNS, resulting in a steady-state of lowered serotonin turnover and degradation by monoamine-oxidase (MAO) enzymes in pre-synaptic or neighboring cells. [less ▲]

Detailed reference viewed: 21 (3 ULg)
Full Text
Peer Reviewed
See detailEffect of antiepileptic drugs and reactive oxygen species on folate receptor 1 (FOLR1)-dependent 5-methyltetrahydrofolate transport.
Opladen, Thomas; Blau, Nenad; RAMAEKERS, Vincent ULg

in Molecular Genetics & Metabolism (2010), 101(1), 48-54

Metabolic breakdown of valproate (VPA), carbamazepine (CBZ) and phenytoin (PHT) by the cytochrome P450 pathway generates toxic drug intermediates and reactive oxygen species (ROS). This mechanism has been ... [more ▼]

Metabolic breakdown of valproate (VPA), carbamazepine (CBZ) and phenytoin (PHT) by the cytochrome P450 pathway generates toxic drug intermediates and reactive oxygen species (ROS). This mechanism has been suspected to play a role in the pathogenesis of secondary cerebral folate deficiency (CFD). Using KB-cell cultures, highly expressing the folate receptor 1 (FOLR1), the effect of antiepileptic drugs (AEDs) and reactive oxygen species (ROS) on the FOLR1 dependent 5-methyltetrahydrofolate (MTHF) uptake was studied. MTHF uptake is time and concentration dependent and shows saturation kinetics. At physiological MTHF concentrations the high-affinity FOLR1 represents the predominant mechanism for cellular incorporation, while at high MTHF concentrations other transport mechanisms participate in folate uptake. Exposure to PHT for more than 8h led to a higher MTHF uptake and decreased cell count, whereas MTHF uptake remained unaltered by VPA and CBZ. However, exposure to superoxide and hydrogen peroxide radicals significantly decreased cellular MTHF uptake. By specific elimination and downregulation of FOLR1 using phosphatidyl-inositol-specific phospholipase C (PIPLC) and siRNA silencing, it was shown that ROS not only inhibited FOLR1 mediated MTHF uptake but also affected all other mechanisms of membrane-mediated MTHF uptake. Generation of ROS with the use of AED might therefore provide an additional explanation for the disturbed folate transfer across the blood-CSF barrier in patients with CFD. [less ▲]

Detailed reference viewed: 10 (1 ULg)
Full Text
Peer Reviewed
See detailCerebral folate deficiency and CNS inflammatory markers in Alpers disease.
Hasselmann, Oswald; Blau, Nenad; RAMAEKERS, Vincent ULg et al

in Molecular Genetics & Metabolism (2010), 99(1), 58-61

We describe a 3.5-year-old female with Alpers disease with a POLG genotype of p.A467T/p.G848S and with a lethal outcome. Laboratory investigation revealed elevated CSF neopterin, IL-6, IL-8, IFN-gamma ... [more ▼]

We describe a 3.5-year-old female with Alpers disease with a POLG genotype of p.A467T/p.G848S and with a lethal outcome. Laboratory investigation revealed elevated CSF neopterin, IL-6, IL-8, IFN-gamma, reduced CSF 5-methyltetrahydrofolate (5MTHF), and increased serum as well as CSF folate receptor blocking autoantibodies. Treatment with oral Leucovorine (5-formyl-tetrahydrofolate) was initiated at 0.25mg/kg bid, and later increased to 4mg/kg bid. Under treatment CSF levels of 5MTHF, seizure frequency and communicative abilities improved. Over a time span of 17months, CSF levels of IL-6 and IFN-gamma decreased, levels of folate receptor blocking autoantibodies continued to raise, whereas CSF IL-8 remained elevated 1500-fold above normal. The child died without apparent stress at the age of 5.5years. Alpers disease, a neurodegenerative disease usually presents in the first years of life as a progressive encephalopathy with multifocal myoclonic seizures, developmental regression, cortical blindness and early death. The underlying genetic defect has been attributed to mutations of the catalytic subunit of the mitochondrial DNA polymerase-gamma leading to an organ-specific mitochondrial DNA depletion syndrome with reduced activity of respiratory chain enzyme complexes in the brain and the liver. A curative therapy is not available. This case report of Alpers disease provides new insights into the pathophysiology of Alpers disease, where mitochondrial dysfunction in conjunction with inflammatory cytokines and blocking folate receptor autoantibodies may lead to a secondary cerebral folate deficiency syndrome. The treatment of the latter provides relief to the patient without stopping the underlying disease. [less ▲]

Detailed reference viewed: 10 (1 ULg)
Full Text
Peer Reviewed
See detailSeizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10.
Scholl, Ute I; Choi, Murim; Liu, Tiewen et al

in Proceedings of the National Academy of Sciences of the United States of America (2009), 106(14), 5842-7

We describe members of 4 kindreds with a previously unrecognized syndrome characterized by seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (hypokalemia, metabolic ... [more ▼]

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, and hypomagnesemia). By analysis of linkage we localize the putative causative gene to a 2.5-Mb segment of chromosome 1q23.2-23.3. Direct DNA sequencing of KCNJ10, which encodes an inwardly rectifying K(+) channel, identifies previously unidentified missense or nonsense mutations on both alleles in all affected subjects. These mutations alter highly conserved amino acids and are absent among control chromosomes. Many of these mutations have been shown to cause loss of function in related K(+) channels. These findings demonstrate that loss-of-function mutations in KCNJ10 cause this syndrome, which we name SeSAME. KCNJ10 is expressed in glia in the brain and spinal cord, where it is believed to take up K(+) released by neuronal repolarization, in cochlea, where it is involved in the generation of endolymph, and on the basolateral membrane in the distal nephron. We propose that KCNJ10 is required in the kidney for normal salt reabsorption in the distal convoluted tubule because of the need for K(+) recycling across the basolateral membrane to enable normal activity of the Na(+)-K(+)-ATPase; loss of this function accounts for the observed electrolyte defects. Mice deficient for KCNJ10 show a related phenotype with seizures, ataxia, and hearing loss, further supporting KCNJ10's role in this syndrome. These findings define a unique human syndrome, and establish the essential role of basolateral K(+) channels in renal electrolyte homeostasis. [less ▲]

Detailed reference viewed: 11 (2 ULg)
Full Text
Peer Reviewed
See detailA milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome
Ramaekers, Vincent ULg; Sequeira, J. M.; Blau, N. et al

in Developmental Medicine and Child Neurology (2008), 50(5), 346-352

In cerebral folate deficiency syndrome, the presence of autoantibodies against the folate receptor (FR) explains decreased folate transport to the central nervous system and the clinical response to ... [more ▼]

In cerebral folate deficiency syndrome, the presence of autoantibodies against the folate receptor (FR) explains decreased folate transport to the central nervous system and the clinical response to folinic acid. Autoantibody crossreactivity with milk FR from different species prompted us to test the effect of a milk-free diet. Intervention with a milkfree diet in 12 children (nine males, three females; mean age 6y [SD 4y 11mo], range 1-19y), decreased autoantibody titer significantly from 2.08pmol of FR blocked per ml of serum (SD 2.1; range 0.24-8.35) to 0.35pmol (SD 0.49; range 0-1.32; p=0.012) over 3 to 13 months, whereas FR autoantibody titer increased significantly to 6.53 (SD 6.08; range 0.54-14.07; p=0.013) in nine children who were reexposed to milk for 6 to 14 weeks. In 12 children on a normal diet (eight males, four females; mean age 5y 5mo [SD 4y 1mo], range 1y 6mo-16y 4mo), the antibody titer increased significantly from 0.84pmol of FR blocked per ml (SD 0.39; range 0.24-1.44) to 3.04pmol (SD 1.42; range 0.84-6.01; p=0.001) over 10 to 24 months. Decreasing the autoantibody titer with a milk-free diet in conjunction with folinic acid therapy may be advocated for these patients. © 2008 Blackwell Publishing Ltd. [less ▲]

Detailed reference viewed: 8 (0 ULg)
Full Text
Peer Reviewed
See detailMitochondrial diseases associated with cerebral folate deficiency
Garcia-Cazorla, A.; Quadros, E. V.; Nascimento, A. et al

in Neurology (2008), 70(16), 1360-1362

Detailed reference viewed: 12 (1 ULg)
Full Text
Peer Reviewed
See detailProgressive encephalopathy in a child with cerebral folate deficiency syndrome.
Bonkowsky, Joshua L; RAMAEKERS, Vincent ULg; Quadros, Edward V et al

in Journal of Child Neurology (2008), 23(12), 1460-3

Cerebral folate deficiency syndrome, a recently recognized cause of developmental delay, regression, and seizures, is associated with autoantibodies against folate receptors. A female child with ... [more ▼]

Cerebral folate deficiency syndrome, a recently recognized cause of developmental delay, regression, and seizures, is associated with autoantibodies against folate receptors. A female child with developmental delay and a history of seizures who presented with seizures and unexplained coma is reported. Extensive testing to evaluate the patient's coma and subsequent developmental regression were unrevealing until the results of her cerebrospinal fluid neurotransmitter analysis returned. These showed low levels of methyltetrahydrofolate, the active metabolite of folate in the cerebrospinal fluid; subsequently, elevated titers of autoantibodies against folate receptors were found. Despite treatment with folinic acid, she developed intractable epilepsy and severe developmental delay. [less ▲]

Detailed reference viewed: 14 (1 ULg)
Full Text
Peer Reviewed
See detailFolate receptor autoimmunity and cerebral folate deficiency in low-functioning autism with neurological deficits
RAMAEKERS, Vincent ULg; Blau, N.; Sequeira, J. M. et al

in Neuropediatrics (2007), 38(6), 276-281

Reduced folate transport to the CNS was identified in two autism spectrum disorders, i.e., Rett syndrome and infantile low-functioning autism with neurological abnormalities. Twenty-five patients with ... [more ▼]

Reduced folate transport to the CNS was identified in two autism spectrum disorders, i.e., Rett syndrome and infantile low-functioning autism with neurological abnormalities. Twenty-five patients with early-onset low-functioning autism with or without neurological deficits, were evaluated for serum folate, cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF), and serum FR autoantibodies of the blocking type to determine the significance of folate receptor (FR) autoantibodies with respect to folate transport across the blood-CSF barrier. In spite of normal serum folate, CSF 5MTHF was low in 23 of 25 patients. The reduced CSF folate in 19 of these 23 patients could be explained by serum FR autoantibodies blocking the folate binding site of the membrane-attached FR on the choroid epithelial cells. Oral folinic acid supplements led to normal CSF 5MTHF and partial or complete clinical recovery after 12 months. Serum FR autoimmunity appears to represent an important factor in the pathogenesis of reduced folate transport to the nervous system among children with early-onset low-functioning autism associated with or without neurological deficits. Early detection of FR autoantibodies may be a key factor in the prevention and therapeutic intervention among this subgroup of patients with autism. © Georg Thieme Verlag KG Stuttgart. [less ▲]

Detailed reference viewed: 35 (1 ULg)
Full Text
Peer Reviewed
See detailFolate receptor autoantibodies and spinal fluid 5-methyltetrahydrofolate deficiency in Rett syndrome
Ramaekers, Vincent ULg; Sequeira, J. M.; Artuch, R. et al

in Neuropediatrics (2007), 38(4), 179-183

Rett syndrome was associated with low cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF) in 42-50% of European patients whereas approximately 93% of the patients from North-America had a normal ... [more ▼]

Rett syndrome was associated with low cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF) in 42-50% of European patients whereas approximately 93% of the patients from North-America had a normal CSF 5MTHF status. We determined the CSF folate status in Rett patients living in North- and South-Western Europe and measured serum folate receptor (FR) autoantibodies of the blocking type to explain the reduced folate transport across the choroid plexus. Irrespective of their MECP2 genotype and despite normal plasma folate values, 14 of 33 Rett patients (42%) had low CSF folate levels. Blocking FR autoantibodies were found in 8 of the Rett patients (24%), 6 of whom had low CSF folate levels. FR autoimmunity was primarily found within the group of Rett patients with low CSF folate status with a higher incidence in North-Western Europe. In Rett patients from North-America 74 of 76 girls had higher folate values in both serum and CSF than European patients. The food folate fortification in North-America may account for the higher folate levels and may prevent CFD in these Rett patients. FR autoimmunity occurred predominantly in Rett patients from North-Western Europe and may contribute to cerebral folate deficiency (CFD). © Georg Thieme Verlag KG Stuttgart. [less ▲]

Detailed reference viewed: 4 (1 ULg)
Full Text
Peer Reviewed
See detailMitochondrial complex I encephalomyopathy and cerebral 5-methyltetrahydrofolate deficiency
RAMAEKERS, Vincent ULg; Wels, J.; Sequeira, J. M. et al

in Neuropediatrics (2007), 38(4), 184-187

Folate transport to the brain depends on ATP-driven folate receptor-mediated transport across choroid plexus epithelial cells. Failure of ATP production in Kearns-Sayre syndrome syndrome provides one ... [more ▼]

Folate transport to the brain depends on ATP-driven folate receptor-mediated transport across choroid plexus epithelial cells. Failure of ATP production in Kearns-Sayre syndrome syndrome provides one explanation for the finding of low spinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF) levels in this condition. Therefore, we suspect the presence of reduced folate transport across the blood-spinal fluid barrier in other mitochondrial encephalopathies. In the present patient with mitochondrial complex I encephalomyopathy a low 5-methyltetrahydrofolate level was found in the CSF. Serum folate receptor autoantibodies were negative and could not explain the low spinal fluid folate levels. The epileptic seizures did not respond to primidone monotherapy, but addition of ubiquinone-10 and radical scavengers reduced seizure frequency. Add-on treatment with folinic acid led to partial clinical improvement including full control of epilepsy, followed by marked recovery from demyelination of the brainstem, thalamus, basal ganglia and white matter. Cerebral folate deficiency is not only present in Kearns-Sayre syndrome but may also be secondary to the failure of mitochondrial ATP production in other mitochondrial encephalopathies. Treatment with folinic acid in addition to supplementation with radical scavengers and cofactors of deficient respiratory enzymes can result in partial clinical improvement and reversal of abnormal myelination patterns on neuro-imaging. © Georg Thieme Verlag KG Stuttgart. [less ▲]

Detailed reference viewed: 11 (1 ULg)
Full Text
Peer Reviewed
See detailAnalysis of 5-methyltetrahydrofolate in serum of healthy children
Opladen, Thomas; Ramaekers, Vincent ULg; Heimann, Gerhard et al

in Molecular genetics and metabolism (2006), 87(1), 61-5

5-Methyltetrahydrofolate (5MTHF) is the active one-carbon donor and the principal circulating form of plasma folates. It is involved in a number of metabolic and neurodevelopmental processes and analysis ... [more ▼]

5-Methyltetrahydrofolate (5MTHF) is the active one-carbon donor and the principal circulating form of plasma folates. It is involved in a number of metabolic and neurodevelopmental processes and analysis of cerebrospinal fluid (CSF) 5MTHF is of great importance in the diagnosis of cerebral folate deficiency (CFD). Serum 5MTHF levels and the 5MTHF serum/CSF ratio may be important additional parameters for the understanding of CFD. We developed a HPLC method for the measurement of 5MTHF in serum and established reference values for the pediatric population. Serum samples from 64 healthy children were extracted with Sep-Pak C18 cartridges and 5MTHF was separated by RP-HPLC and quantified by electrochemical detection. 5MTHF was separated from other folates and detected after 8.7 min with linearity of up to 1600 nmol/L. The detection limit was 4.5 nmol/L and recovery during solid-phase extraction for low and high concentrations of 5MTHF was 66 and 62%, respectively. Within-run imprecision (13.5%) was slightly higher than run-to-run imprecision (8.5%). 5MTHF levels in healthy children were found to be age-dependent, decreasing from 158.0 nmol/L in newborns to 60.1 nmol/L in children older than 16 years. The method we describe is sensitive, selective, and reliable for the analysis of 5MTHF from 400 microL of serum. [less ▲]

Detailed reference viewed: 4 (0 ULg)
Full Text
Peer Reviewed
See detailAutoantibodies to folate receptors in the cerebral folate deficiency syndrome
Ramaekers, Vincent ULg; Rothenberg, S. P.; Sequeira, J. M. et al

in New England Journal of Medicine (2005), 352(19), 1985-1991

In infantile-onset cerebral folate deficiency, 5-methyltetrahydrofolate (5MTHF) levels in the cerebrospinal fluid are low, but folate levels in the serum and erythrocytes are normal. We examined serum ... [more ▼]

In infantile-onset cerebral folate deficiency, 5-methyltetrahydrofolate (5MTHF) levels in the cerebrospinal fluid are low, but folate levels in the serum and erythrocytes are normal. We examined serum specimens from 28 children with cerebral folate deficiency, 5 of their mothers, 28 age-matched control subjects, and 41 patients with an unrelated neurologic disorder. Serum from 25 of the 28 patients and 0 of 28 control subjects contained high-affinity blocking autoantibodies against membrane-bound folate receptors that are present on the choroid plexus. Oral folinic acid normalized 5MTHF levels in the cerebrospinal fluid and led to clinical improvement. Cerebral folate deficiency is a disorder in which autoantibodies can prevent the transfer of folate from the plasma to the cerebrospinal fluid. Copyright © 2005 Massachusetts Medical Society. [less ▲]

Detailed reference viewed: 4 (0 ULg)
Full Text
Peer Reviewed
See detailCerebral folate deficiency with developmental delay, autism, and response to folinic acid
Moretti, P.; Sahoo, T.; Hyland, K. et al

in Neurology (2005), 64(6), 1088-1090

The authors describe a 6-year-old girl with developmental delay, psychomotor regression, seizures, mental retardation, and autistic features associated with low CSF levels of 5-methyltetrahydrofolate, the ... [more ▼]

The authors describe a 6-year-old girl with developmental delay, psychomotor regression, seizures, mental retardation, and autistic features associated with low CSF levels of 5-methyltetrahydrofolate, the biologically active form of folates in CSF and blood. Folate and B12 levels were normal in peripheral tissues, suggesting cerebral Mate deficiency. Treatment with folinic acid corrected CSF abnormalities and improved motor skills. Copyright © 2005 by AAN Enterprises, Inc. [less ▲]

Detailed reference viewed: 4 (0 ULg)
Full Text
Peer Reviewed
See detailWhite-matter disease in 18q deletion (18q-) syndrome: magnetic resonance spectroscopy indicates demyelination or increased myelin turnover rather than dysmyelination.
Hausler, M.; Anhuf, D.; Schuler, H. et al

in Neuroradiology (2005), 47(1), 83-6

Proton magnetic resonance spectroscopic data ((1)H-MR spectroscopy) of patients with 18q deletion syndrome have not yet been reported. (1)H-MR spectroscopy, performed in an affected 2-year-old girl with ... [more ▼]

Proton magnetic resonance spectroscopic data ((1)H-MR spectroscopy) of patients with 18q deletion syndrome have not yet been reported. (1)H-MR spectroscopy, performed in an affected 2-year-old girl with markedly delayed neuromotor development and typical supratentorial white-matter disease (WMD), showed an increase of choline and alpha-glutamate concentrations. Eight months later, simultaneously with clinical improvement, alpha-glutamate had normalised whereas choline remained slightly increased. Active demyelination or increased myelin turnover might contribute to the hitherto unexplained WMD of this rare disorder. [less ▲]

Detailed reference viewed: 6 (0 ULg)