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Auteur Jeffrey M. SEQUEIRA |
Documents disponibles écrits par cet auteur (2)
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Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial / Vincent Th. RAMAEKERS in Autism Research and Treatment, 2019 (2019)
[article]
Titre : Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial Type de document : Texte imprimé et/ou numérique Auteurs : Vincent Th. RAMAEKERS, Auteur ; Jeffrey M. SEQUEIRA, Auteur ; Marco DIDUCA, Auteur ; Géraldine VRANCKEN, Auteur ; Aurore THOMAS, Auteur ; Céline PHILIPPE, Auteur ; Marie PETERS, Auteur ; Annick JADOT, Auteur ; Edward V. QUADROS, Auteur Article en page(s) : 12p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background. In contrast to multiple rare monogenetic abnormalities, a common biomarker among children with infantile autism and their parents is the discovery of serum autoantibodies directed to the folate receptor alpha (FR?) localized at blood-brain and placental barriers, impairing physiologic folate transfer to the brain and fetus. Since outcome after behavioral intervention remains poor, a trial was designed to treat folate receptor alpha (FR?) autoimmunity combined with correction of deficient nutrients due to abnormal feeding habits. Methods. All participants with nonsyndromic infantile autism underwent a routine protocol measuring CBC, iron, vitamins, coenzyme Q10, metals, and trace elements. Serum FR? autoantibodies were assessed in patients, their parents, and healthy controls. A self-controlled therapeutic trial treated nutritional derangements with addition of high-dose folinic acid if FR? autoantibodies tested positive. The Childhood Autism Rating Scale (CARS) monitored at baseline and following 2 years of treatment was compared to the CARS of untreated autistic children serving as a reference. Results. In this self-controlled trial (82 children; mean age ± SD: 4.4 ± 2.3 years; male:female ratio: 4.8:1), FR? autoantibodies were found in 75.6 % of the children, 34.1 % of mothers, and 29.4 % of fathers versus 3.3 % in healthy controls. Compared to untreated patients with autism (n=84) whose CARS score remained unchanged, a 2-year treatment decreased the initial CARS score from severe (mean ± SD: 41.34 ± 6.47) to moderate or mild autism (mean ± SD: 34.35 ± 6.25; paired t-test p<0.0001), achieving complete recovery in 17/82 children (20.7 %). Prognosis became less favorable with the finding of higher FR? autoantibody titers, positive maternal FR? autoantibodies, or FR? antibodies in both parents. Conclusions. Correction of nutritional deficiencies combined with high-dose folinic acid improved outcome for autism, although the trend of a poor prognosis due to maternal FR? antibodies or FR? antibodies in both parents may warrant folinic acid intervention before conception and during pregnancy. En ligne : https://doi.org/10.1155/2019/7486431 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402
in Autism Research and Treatment > 2019 (2019) . - 12p.[article] Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial [Texte imprimé et/ou numérique] / Vincent Th. RAMAEKERS, Auteur ; Jeffrey M. SEQUEIRA, Auteur ; Marco DIDUCA, Auteur ; Géraldine VRANCKEN, Auteur ; Aurore THOMAS, Auteur ; Céline PHILIPPE, Auteur ; Marie PETERS, Auteur ; Annick JADOT, Auteur ; Edward V. QUADROS, Auteur . - 12p.
Langues : Anglais (eng)
in Autism Research and Treatment > 2019 (2019) . - 12p.
Index. décimale : PER Périodiques Résumé : Background. In contrast to multiple rare monogenetic abnormalities, a common biomarker among children with infantile autism and their parents is the discovery of serum autoantibodies directed to the folate receptor alpha (FR?) localized at blood-brain and placental barriers, impairing physiologic folate transfer to the brain and fetus. Since outcome after behavioral intervention remains poor, a trial was designed to treat folate receptor alpha (FR?) autoimmunity combined with correction of deficient nutrients due to abnormal feeding habits. Methods. All participants with nonsyndromic infantile autism underwent a routine protocol measuring CBC, iron, vitamins, coenzyme Q10, metals, and trace elements. Serum FR? autoantibodies were assessed in patients, their parents, and healthy controls. A self-controlled therapeutic trial treated nutritional derangements with addition of high-dose folinic acid if FR? autoantibodies tested positive. The Childhood Autism Rating Scale (CARS) monitored at baseline and following 2 years of treatment was compared to the CARS of untreated autistic children serving as a reference. Results. In this self-controlled trial (82 children; mean age ± SD: 4.4 ± 2.3 years; male:female ratio: 4.8:1), FR? autoantibodies were found in 75.6 % of the children, 34.1 % of mothers, and 29.4 % of fathers versus 3.3 % in healthy controls. Compared to untreated patients with autism (n=84) whose CARS score remained unchanged, a 2-year treatment decreased the initial CARS score from severe (mean ± SD: 41.34 ± 6.47) to moderate or mild autism (mean ± SD: 34.35 ± 6.25; paired t-test p<0.0001), achieving complete recovery in 17/82 children (20.7 %). Prognosis became less favorable with the finding of higher FR? autoantibody titers, positive maternal FR? autoantibodies, or FR? antibodies in both parents. Conclusions. Correction of nutritional deficiencies combined with high-dose folinic acid improved outcome for autism, although the trend of a poor prognosis due to maternal FR? antibodies or FR? antibodies in both parents may warrant folinic acid intervention before conception and during pregnancy. En ligne : https://doi.org/10.1155/2019/7486431 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402 Oxidative Stress, Folate Receptor Autoimmunity, and CSF Findings in Severe Infantile Autism / Vincent T. RAMAEKERS in Autism Research and Treatment, 2020 (2020)
[article]
Titre : Oxidative Stress, Folate Receptor Autoimmunity, and CSF Findings in Severe Infantile Autism Type de document : Texte imprimé et/ou numérique Auteurs : Vincent T. RAMAEKERS, Auteur ; Jeffrey M. SEQUEIRA, Auteur ; Beat THÖNY, Auteur ; Edward V. QUADROS, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background. Biomarkers such as oxidative stress, folate receptor alpha (FR?) autoimmunity, and abnormal brain serotonin turnover are common in autism. Methods. Oxidative stress biomarkers with pro- and antioxidants were measured in the severe form of infantile autism (n = 38) and controls (n = 24). Children and parents had repeated testing for serum FR autoantibodies, spinal fluid dopamine and serotonin metabolites, pterins, and N5-methyltetrahydrofolate (MTHF). Statistical analysis assessed correlations between variables. Genetic analysis included the SLC6A4 and SLC29A4 genes encoding synaptic serotonin reuptake proteins. Results. Compared to controls, the autism group showed a significant increase in oxidative DNA damage in lymphocytes, plasma ceruloplasmin and copper levels with a high copper/zinc ratio, thiol proteins, and superoxide dismutase (SOD) activity. Vitamin C levels were significantly diminished. In most autistic patients, the vitamin A (64%) and D (70%) levels were low. Serum FR autoantibodies fluctuating over 5 7 week periods presented in 68% of all autistic children, 41% of parents vs. 3.3% of control children and their parents. CSF showed lowered serotonin 5-hydroxyindole acetic acid (5HIAA) metabolites in 13 (34%), a low 5HIAA to HVA (dopamine metabolite) ratio in 5 (13%), low 5HIAA and MTHF in 2 (5%), and low MTHF in 8 patients (21%). A known SLC6A4 mutation was identified only in 1 autistic child with low CSF 5HIAA and a novel SLC29A4 mutation was identified in identical twins. Low CSF MTHF levels among only 26% of subjects can be explained by the fluctuating FR antibody titers. Two or more aberrant pro-oxidant and/or antioxidant factors predisposed to low CSF serotonin metabolites. Three autistic children having low CSF 5HIAA and elevated oxidative stress received antioxidative supplements followed by CSF 5HIAA normalisation. Conclusion. In autism, we found diverse combinations for FR autoimmunity and/or oxidative stress, both amenable to treatment. Parental and postnatal FR autoantibodies tend to block folate passage to the brain affecting folate-dependent pathways restored by folinic acid treatment, while an abnormal redox status tends to induce reduced serotonin turnover, corrected by antioxidant therapy. Trial Registration. The case-controlled study was approved in 2008 by the IRB at Liège University (Belgian Number: "http://clinicaltrial.gov/ct2/show/B70720083916"). Lay Summary. Children with severe infantile autism frequently have serum folate receptor autoantibodies that block the transport of the essential vitamin folate across the blood-brain barrier to the brain. Parents are often asymptomatic carriers of these serum folate receptor autoantibodies, which in mothers can block folate passage across the placenta to their unborn child. This folate deficiency during the child’s intrauterine development may predispose to neural tube defects and autism. Oxidative stress represents a condition with the presence of elevated toxic oxygen derivatives attributed to an imbalance between the formation and protection against these toxic reactive oxygen derivatives. Oxidative stress was found to be present in autistic children where these reactive oxygen derivatives can cause damage to DNA, which changes DNA function and regulation of gene expression. In addition, excessive amounts of these toxic oxygen derivatives are likely to damage the enzyme producing the neuromessenger serotonin in the brain, diminished in about 1/3 of the autistic children. Testing children with autism for oxidative stress and its origin, as well as testing for serum folate receptor autoantibodies, could open new approaches towards more effective treatments. En ligne : https://doi.org/10.1155/2020/9095284 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438
in Autism Research and Treatment > 2020 (2020)[article] Oxidative Stress, Folate Receptor Autoimmunity, and CSF Findings in Severe Infantile Autism [Texte imprimé et/ou numérique] / Vincent T. RAMAEKERS, Auteur ; Jeffrey M. SEQUEIRA, Auteur ; Beat THÖNY, Auteur ; Edward V. QUADROS, Auteur.
Langues : Anglais (eng)
in Autism Research and Treatment > 2020 (2020)
Index. décimale : PER Périodiques Résumé : Background. Biomarkers such as oxidative stress, folate receptor alpha (FR?) autoimmunity, and abnormal brain serotonin turnover are common in autism. Methods. Oxidative stress biomarkers with pro- and antioxidants were measured in the severe form of infantile autism (n = 38) and controls (n = 24). Children and parents had repeated testing for serum FR autoantibodies, spinal fluid dopamine and serotonin metabolites, pterins, and N5-methyltetrahydrofolate (MTHF). Statistical analysis assessed correlations between variables. Genetic analysis included the SLC6A4 and SLC29A4 genes encoding synaptic serotonin reuptake proteins. Results. Compared to controls, the autism group showed a significant increase in oxidative DNA damage in lymphocytes, plasma ceruloplasmin and copper levels with a high copper/zinc ratio, thiol proteins, and superoxide dismutase (SOD) activity. Vitamin C levels were significantly diminished. In most autistic patients, the vitamin A (64%) and D (70%) levels were low. Serum FR autoantibodies fluctuating over 5 7 week periods presented in 68% of all autistic children, 41% of parents vs. 3.3% of control children and their parents. CSF showed lowered serotonin 5-hydroxyindole acetic acid (5HIAA) metabolites in 13 (34%), a low 5HIAA to HVA (dopamine metabolite) ratio in 5 (13%), low 5HIAA and MTHF in 2 (5%), and low MTHF in 8 patients (21%). A known SLC6A4 mutation was identified only in 1 autistic child with low CSF 5HIAA and a novel SLC29A4 mutation was identified in identical twins. Low CSF MTHF levels among only 26% of subjects can be explained by the fluctuating FR antibody titers. Two or more aberrant pro-oxidant and/or antioxidant factors predisposed to low CSF serotonin metabolites. Three autistic children having low CSF 5HIAA and elevated oxidative stress received antioxidative supplements followed by CSF 5HIAA normalisation. Conclusion. In autism, we found diverse combinations for FR autoimmunity and/or oxidative stress, both amenable to treatment. Parental and postnatal FR autoantibodies tend to block folate passage to the brain affecting folate-dependent pathways restored by folinic acid treatment, while an abnormal redox status tends to induce reduced serotonin turnover, corrected by antioxidant therapy. Trial Registration. The case-controlled study was approved in 2008 by the IRB at Liège University (Belgian Number: "http://clinicaltrial.gov/ct2/show/B70720083916"). Lay Summary. Children with severe infantile autism frequently have serum folate receptor autoantibodies that block the transport of the essential vitamin folate across the blood-brain barrier to the brain. Parents are often asymptomatic carriers of these serum folate receptor autoantibodies, which in mothers can block folate passage across the placenta to their unborn child. This folate deficiency during the child’s intrauterine development may predispose to neural tube defects and autism. Oxidative stress represents a condition with the presence of elevated toxic oxygen derivatives attributed to an imbalance between the formation and protection against these toxic reactive oxygen derivatives. Oxidative stress was found to be present in autistic children where these reactive oxygen derivatives can cause damage to DNA, which changes DNA function and regulation of gene expression. In addition, excessive amounts of these toxic oxygen derivatives are likely to damage the enzyme producing the neuromessenger serotonin in the brain, diminished in about 1/3 of the autistic children. Testing children with autism for oxidative stress and its origin, as well as testing for serum folate receptor autoantibodies, could open new approaches towards more effective treatments. En ligne : https://doi.org/10.1155/2020/9095284 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438