Cerebral Folate Deficiency (CFD)
Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in autism spectrum disorder (ASD). They disrupt the transportation of folate across the blood-brain barrier by binding to the FRα. Children with ASD and FRAAs have been reported to respond well to treatment with a form of folate known as folinic acid, suggesting that they may be an important ASD subgroup to identify and treat.
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Published Articles
Results are displayed in descending order beginning with most recent publications.
Folate Receptor Alpha Autoantibodies in the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Population
Wells, L.; O’Hara, N.; Frye, R.E.; Hullavard, N.; Smith, E. J. Pers. Med. 2024, 14, 166.
Binding Folate Receptor Alpha Autoantibody Is a Biomarker for Leucovorin Treatment Response in Autism Spectrum Disorder
Frye RE, McCarty PJ, Werner BA, Scheck AC, Collins HL, Adelman SJ, Rossignol DA, Quadros EV. J Pers Med. 1 Jan 2024.
Is a Folate Deficiency Worsening Your Child’s Autism?
Posted by: Potomac Psychiatry
Posted on: April 13, 2023
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The Soluble Folate Receptor in Autism Spectrum Disorder: Relation to Autism Severity and Leucovorin Treatment.
Frye RE, Lane A, Worner A, Werner BA, McCarty PJ, Scheck AC, Collins HL, Adelman SJ, Quadros EV, Rossignol DA. J Pers Med. 2022 Dec 8;12(12):2033. doi: 10.3390/jpm12122033. PMID: 36556254; PMCID: PMC9786140.
Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis
Rossignol DA, Frye RE. J Pers Med. 2021 Nov 3;11(11):1141. doi: 10.3390/jpm11111141. Erratum in: J Pers Med. 2022 Apr 29;12(5): PMID: 34834493; PMCID: PMC8622150.
Treatment of Folate Metabolism Abnormalities in Autism Spectrum Disorder
Frye RE, Rossignol DA, Scahill L, McDougle CJ, Huberman H, Quadros EV. Semin Pediatr Neurol. 2020 Oct;35:100835. doi: 10.1016/j.spen.2020.100835. Epub 2020 Jun 25. PMID: 32892962; PMCID: PMC7477301.
Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial
Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, Tippett M, Sailey A, Wynne R, Rose S, Melnyk S, Jill James S, Sequeira JM, Quadros EV. Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Mol Psychiatry. 2018 Feb;23(2):247-256. doi: 10.1038/mp.2016.168. Epub 2016 Oct 18. PMID: 27752075; PMCID: PMC5794882.
Treatment with folate in autism spectrum disorder Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial.
Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, Tippett M, Sailey A, Wynne R, Rose S, Melnyk S, Jill James S, Sequeira JM, Quadros EV. Mol Psychiatry. 2018; 23(2):247-256.
Folate metabolism abnormalities in autism: potential biomarkers
Frye RE, Slattery JC, Quadros EV. Biomark Med. 2017 Aug;11(8):687-699. doi: 10.2217/bmm-2017-0109. Epub 2017 Aug 3. PMID: 28770615.
Thyroid dysfunction in children withautism spectrum disorder is associated with folate receptor α autoimmune disorder.
Frye RE, Wynne R, Rose S, Slattery J, Delhey L, Tippett M, Kahler SG, Bennuri SC, Melnyk S, Sequeira JM, Quadros EV. J Neuroendocrinol. 2017; 29(3).
Blocking and Binding Folate Receptor Alpha Autoantibodies Identify Novel Autism Spectrum Disorder Subgroups
Frye RE, Delhey L, Slattery J, Tippett M, Wynne R, Rose S, Kahler SG, Bennuri SC, Melnyk S, Sequeira JM, Quadros E. Front Neurosci. 2016; 10:80.
Effectiveness of methylcobalamin and folinic Acid treatment on adaptive behavior in children with autistic disorder is related to glutathione redox status
Frye RE, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW, Walters L, James SJ. Effectiveness of methylcobalamin and folinic Acid treatment on adaptive behavior in children with autistic disorder is related to glutathione redox status. Autism Res Treat. 2013;2013:609705. doi: 10.1155/2013/609705. Epub 2013 Oct 12. PMID: 24224089; PMCID: PMC3810468.
Cerebral folate receptor autoantibodies in autism spectrum disorder.
Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. Mol Psychiatry. 2013; 18(3):369-81.
Other Resources
CEREBRAL FOLATE DEFICIENCY IN ASD
from The Journal of Autismone
CENTRAL FOLATE ABNORMALITIES
from Autism File
Folate Receptor Alpha Autoantibodies in the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Population
Wells, L.; O’Hara, N.; Frye, R.E.; Hullavard, N.; Smith, E. J. Pers. Med. 2024, 14, 166.
Binding Folate Receptor Alpha Autoantibody Is a Biomarker for Leucovorin Treatment Response in Autism Spectrum Disorder
Frye RE, McCarty PJ, Werner BA, Scheck AC, Collins HL, Adelman SJ, Rossignol DA, Quadros EV. J Pers Med. 1 Jan 2024.
Is a Folate Deficiency Worsening Your Child’s Autism?
Posted by: Potomac Psychiatry
Posted on: April 13, 2023
Read Now
Levoleucovorin Treatment for Autism
Title: Levoleucovorin Treatment for Autism
Date: December 2022
Location: Synchrony 2022 – The BRAIN Foundation
Presented by: Dr. Richard Frye, MD PhD
Cerebral Folate Metabolism Presentation
Title: Cerebral Folate Metabolism Abnormalities in Neurodevelopmental Disorders
Date: July 1, 2022
Location: SEECA
Presented by: Dr. Richard Frye, MD PhD
Phoenix doctor’s treatment helps speech and communication for kids with autism
Posted by: KPHO/KTVK Nightly News
Posted on: September 17, 2021
Watch Video
Live interview with Dr. Richard Frye
Title: Interview/Live Chat
Date: May 14, 2021
Location: Autism Research Coalition Online
Featuring: Dr. Richard Frye, MD PhD
Autism & Folate Presentation
Title: Autism & Folate
Date: April 25, 2019
Location: Autism Hope Alliance
Presented by: Dr. Richard Frye, MD PhD
Folate Metabolism, Mitochondrial Disease and ASD
Title: Folate Metabolism, Mitochondrial Disease and ASD
Date: March 1, 2017
Location: Autism Research Institute
Presented by: Dr. Richard Frye, MD PhD
Folinic Acid May Improve Verbal Skills in Children With ASD
By Nick Zagorski
Posted: December 2, 2016
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Research Shows Folinic Acid Could Help Autistic Children Communicate Better
Posted by: KUAF
Posted on: October 26, 2016
Open Podcast
Small study finds folinic acid improves communication & eases symptoms of autism
By: Autism Speaks
Posted: October 18, 2016
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Folinic acid could help children with autism communicate better
By: Ryan Maass
Posted: October 18, 2016
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Folinic acid could help children with autism communicate better
By Springer
Posted: October 18, 2016
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Folinic acid could help children with autism communicate better
Peer Reviewed Publication
Journal of Molecular Psychiatry
Published October 18, 2016
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The Families That Launch Their Own Autism Studies
By: Carrie Arnold and Spectrum
Posted: September 30, 2016
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Autism Research Connections #1
Posted by: Autism Research Connection
Posted on: March 15, 2016
Open Podcast
Read Transcripts
N of One: Autism Research Foundation Interviews Richard Frye, MD PhD on Folinic Acid & Autism Trial
By: N of One Autism Research Foundation
2016
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Richard E Frye, MD, PhD. is “All In” for Autistic Children
By: Becky Gillette
Posted: November 11, 2015
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Mito, Autism and Cerebral Folate Deficiency
Posted by: Mito Action
Posted on: June 1, 2012
Open Podcast
Folate Receptor Alpha Autoantibody Test (FRAT)
Folate Receptor Alpha Autoantibody Test (FRAT)
This test measures two proteins in the blood called autoantibodies whichinterfere with the ability of the vitamin folate to be used by the brain and other parts of the body.The two autoantibodies are called ‘blocking’ and ‘blinding’ and then each may be ‘negative’, ‘low’, ‘medium’ or ‘high.’