Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial
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 (FRα) localized at blood-brain and placental barriers, impairing physiologic fo...
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| description | 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 (FRα) 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 (FRα) 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 FRα 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 FRα 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), FRα 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 |
| doi_str_mv | 10.1155/2019/7486431 |
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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 (FRα) 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 (FRα) 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 FRα 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 FRα 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), FRα 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 FRα autoantibody titers, positive maternal FRα autoantibodies, or FRα 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 FRα antibodies or FRα antibodies in both parents may warrant folinic acid intervention before conception and during pregnancy.</description><identifier>ISSN: 2090-1925</identifier><identifier>EISSN: 2090-1933</identifier><identifier>DOI: 10.1155/2019/7486431</identifier><identifier>PMID: 31316831</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Antioxidants ; Autism ; Autoantibodies ; Autoimmunity ; Brain research ; Cell cycle ; Congenital diseases ; Enzymes ; Folic acid ; Gene expression ; Hydrogen peroxide ; Leucovorin ; Medical research ; Medicine, Experimental ; Metabolism ; Neurosciences ; Oxidative stress ; Patient outcomes ; Proteins ; Vitamin B ; Vitamin deficiency</subject><ispartof>Autism Research and Treatment, 2019, Vol.2019 (2019), p.1-12</ispartof><rights>Copyright © 2019 Vincent Th. Ramaekers et al.</rights><rights>COPYRIGHT 2019 John Wiley & Sons, Inc.</rights><rights>Copyright © 2019 Vincent Th. Ramaekers et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2019 Vincent Th. Ramaekers et al. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4141-5c35fecb9d7aef22d47a65ee8e19c725fd780f22d14dfd90af1b6770c39c6e73</citedby><cites>FETCH-LOGICAL-c4141-5c35fecb9d7aef22d47a65ee8e19c725fd780f22d14dfd90af1b6770c39c6e73</cites><orcidid>0000-0003-1076-762X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604479/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604479/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31316831$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Canitano, Roberto</contributor><contributor>Roberto Canitano</contributor><creatorcontrib>Quadros, Edward V.</creatorcontrib><creatorcontrib>Jadot, Annick</creatorcontrib><creatorcontrib>Philippe, Céline</creatorcontrib><creatorcontrib>Thomas, Aurore</creatorcontrib><creatorcontrib>Vrancken, Géraldine</creatorcontrib><creatorcontrib>DiDuca, Marco</creatorcontrib><creatorcontrib>Sequeira, Jeffrey M.</creatorcontrib><creatorcontrib>Ramaekers, Vincent Th</creatorcontrib><creatorcontrib>Peters, Marie</creatorcontrib><title>Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial</title><title>Autism Research and Treatment</title><addtitle>Autism Res Treat</addtitle><description>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 (FRα) 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 (FRα) 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 FRα 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 FRα 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), FRα 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 FRα autoantibody titers, positive maternal FRα autoantibodies, or FRα 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 FRα antibodies or FRα antibodies in both parents may warrant folinic acid intervention before conception and during pregnancy.</description><subject>Antioxidants</subject><subject>Autism</subject><subject>Autoantibodies</subject><subject>Autoimmunity</subject><subject>Brain research</subject><subject>Cell cycle</subject><subject>Congenital diseases</subject><subject>Enzymes</subject><subject>Folic acid</subject><subject>Gene expression</subject><subject>Hydrogen peroxide</subject><subject>Leucovorin</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Metabolism</subject><subject>Neurosciences</subject><subject>Oxidative stress</subject><subject>Patient outcomes</subject><subject>Proteins</subject><subject>Vitamin B</subject><subject>Vitamin deficiency</subject><issn>2090-1925</issn><issn>2090-1933</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNks9rFDEUxwdRbKm9eZaAIIJumx-TmYkHYVmtLhQLuveQzbzspmSSbSbT0oP_uxl33XbFg8khj7zP-ya89y2KlwSfEcL5OcVEnNdlU5WMPCmOKRZ4QgRjT_cx5UfFad9f47wqzErWPC-OGGGkahg5Ln7Ou00Mt9av0NWQdOgAWY_m3iifrAM0HZLtO3Rn0xpdBKcSoO-gYZNCHHPBdt3gbbpHyrfo25CiTTZ45dAniMqvoAOf-g9oin6AM5NZ8CkG56BFi2iVe1E8M8r1cLo7T4rFxefF7Ovk8urLfDa9nOiSlGTCNeMG9FK0tQJDaVvWquIADRCha8pNWzd4vCdla1qBlSHLqq6xZkJXULOT4uNWdjMsO2h1_lNUTm6i7VS8l0FZeZjxdi1X4VZWFS7LWmSBtzuBGG4G6JPsbK_BOeUhDL2klAtBRC2ajL7-C70OQ8wd-U1hXtKa8wdqpRxI603I7-pRVE4rTAnmjNJMnf2DyruFzurgweQRHRa8eVSwBuXSug9uGGfSH4Lvt6COoe8jmH0zCJajs-ToLLlzVsZfPW7gHv7jowy82wJr61t1Z_9TDjIDRj3QhNKSCvYL2w_fGw</recordid><startdate>2019</startdate><enddate>2019</enddate><creator>Quadros, Edward V.</creator><creator>Jadot, Annick</creator><creator>Philippe, Céline</creator><creator>Thomas, Aurore</creator><creator>Vrancken, Géraldine</creator><creator>DiDuca, Marco</creator><creator>Sequeira, Jeffrey M.</creator><creator>Ramaekers, Vincent Th</creator><creator>Peters, Marie</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>88G</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>M2M</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PADUT</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1076-762X</orcidid></search><sort><creationdate>2019</creationdate><title>Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial</title><author>Quadros, Edward V. ; Jadot, Annick ; Philippe, Céline ; Thomas, Aurore ; Vrancken, Géraldine ; DiDuca, Marco ; Sequeira, Jeffrey M. ; Ramaekers, Vincent Th ; Peters, Marie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4141-5c35fecb9d7aef22d47a65ee8e19c725fd780f22d14dfd90af1b6770c39c6e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antioxidants</topic><topic>Autism</topic><topic>Autoantibodies</topic><topic>Autoimmunity</topic><topic>Brain research</topic><topic>Cell cycle</topic><topic>Congenital diseases</topic><topic>Enzymes</topic><topic>Folic acid</topic><topic>Gene expression</topic><topic>Hydrogen peroxide</topic><topic>Leucovorin</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Metabolism</topic><topic>Neurosciences</topic><topic>Oxidative stress</topic><topic>Patient outcomes</topic><topic>Proteins</topic><topic>Vitamin B</topic><topic>Vitamin deficiency</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Quadros, Edward V.</creatorcontrib><creatorcontrib>Jadot, Annick</creatorcontrib><creatorcontrib>Philippe, Céline</creatorcontrib><creatorcontrib>Thomas, Aurore</creatorcontrib><creatorcontrib>Vrancken, Géraldine</creatorcontrib><creatorcontrib>DiDuca, Marco</creatorcontrib><creatorcontrib>Sequeira, Jeffrey M.</creatorcontrib><creatorcontrib>Ramaekers, Vincent Th</creatorcontrib><creatorcontrib>Peters, Marie</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Psychology Database (Alumni)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Psychology Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Research Library China</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Autism Research and Treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Quadros, Edward V.</au><au>Jadot, Annick</au><au>Philippe, Céline</au><au>Thomas, Aurore</au><au>Vrancken, Géraldine</au><au>DiDuca, Marco</au><au>Sequeira, Jeffrey M.</au><au>Ramaekers, Vincent Th</au><au>Peters, Marie</au><au>Canitano, Roberto</au><au>Roberto Canitano</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial</atitle><jtitle>Autism Research and Treatment</jtitle><addtitle>Autism Res Treat</addtitle><date>2019</date><risdate>2019</risdate><volume>2019</volume><issue>2019</issue><spage>1</spage><epage>12</epage><pages>1-12</pages><issn>2090-1925</issn><eissn>2090-1933</eissn><abstract>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 (FRα) 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 (FRα) 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 FRα 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 FRα 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), FRα 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 FRα autoantibody titers, positive maternal FRα autoantibodies, or FRα 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 FRα antibodies or FRα antibodies in both parents may warrant folinic acid intervention before conception and during pregnancy.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>31316831</pmid><doi>10.1155/2019/7486431</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-1076-762X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antioxidants Autism Autoantibodies Autoimmunity Brain research Cell cycle Congenital diseases Enzymes Folic acid Gene expression Hydrogen peroxide Leucovorin Medical research Medicine, Experimental Metabolism Neurosciences Oxidative stress Patient outcomes Proteins Vitamin B Vitamin deficiency |
| title | Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial |
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