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| {{Infobox medical condition (new) | | |
| | name = Cerebral folate deficiency | | {{Infobox medical condition |
| | synonyms = Cerebral folate deficiency syndrome, neurodegeneration due to cerebral folate transport deficiency, cerebral folate transport deficiency, FOLR1 deficiency<ref name=GARD2019>{{cite web |title=Cerebral folate deficiency |url=https://rarediseases.info.nih.gov/diseases/10594/cerebral-folate-deficiency |website=rarediseases.info.nih.gov |accessdate=7 January 2019}}</ref><ref name=GHR2019/> | | | name = Cerebral Folate Deficiency |
| | image = File:5-Methyltetrahydrofolate.png| | | | image = <!-- Image removed --> |
| | width =
| | | caption = <!-- Caption removed --> |
| | alt =
| | | field = Neurology |
| | caption = [[5-methyltetrahydrofolate]] is decreased in concentration in the human brain
| | | symptoms = Developmental delay, movement disorders, seizures |
| | pronounce =
| | | complications = Intellectual disability, autism spectrum disorder |
| | field = | | | onset = Infancy |
| | symptoms = | | | duration = Lifelong |
| | complications = | | | causes = Genetic mutations, autoimmunity |
| | onset = | | | diagnosis = CSF analysis, genetic testing |
| | duration = | | | treatment = Folinic acid supplementation |
| | types =
| | | frequency = Rare |
| | causes = [[Genetic disorder]]<ref name=GHR2019/>, [[autoantibodies]] | |
| | risks =
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| | diagnosis = [[Lumbar puncture]] | |
| | differential =
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| | prevention =
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| | treatment = | |
| | medication = [[Folinic acid]]
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| | prognosis =
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| | frequency = FOLR1 mutation, <20 described cases<ref name=GHR2019/> | |
| | deaths =
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| }} | | }} |
| <!-- Definition and symptoms -->
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| '''Cerebral folate deficiency''' is a condition in which concentrations of [[5-methyltetrahydrofolate]] are low in the [[brain]] as measured in the [[cerebral spinal fluid]] despite being normal in the blood.<ref name=Gordon2009>{{cite journal |last1=Gordon |first1=N |title=Cerebral folate deficiency. |journal=Developmental Medicine and Child Neurology |date=2009 |volume=51 |issue=3 |pages=180–182 |doi=10.1111/j.1469-8749.2008.03185.x |pmid=19260931}}</ref> Symptoms typically appear at about 5 to 24 months of age.<ref name=Gordon2009/><ref name=GHR2019/> Without treatment there may be poor muscle tone, trouble with coordination, trouble talking, and [[seizures]].<ref name=Gordon2009/>
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| <!-- Cause and diagnosis -->
| | '''Cerebral Folate Deficiency''' (CFD) is a neurological disorder characterized by low levels of [[5-methyltetrahydrofolate]] (5-MTHF) in the [[cerebrospinal fluid]] (CSF) despite normal levels of folate in the blood. This condition can lead to a variety of neurological symptoms and developmental issues. |
| One cause of cerebral folate deficiency is a mutation in a [[gene]] responsible for folate transport, specifically [[FOLR1]].<ref name=GHR2019/><ref name="pmid22835503">{{cite journal |vauthors = Serrano M, Pérez-Dueñas B, Montoya J, Ormazabal A, Artuch R |title = Genetic causes of cerebral folate deficiency: clinical, biochemical and therapeutic aspects |journal = Drug Discovery Today |volume = 17 |issue=23–24 |pages=1299–1306 |date=2012 |pmid = 22835503 |pmc = |doi=10.1016/j.drudis.2012.07.008 }}</ref> This is inherited from a person's parents in an [[autosomal recessive]] manner.<ref name=GHR2019/> Other causes appear to be [[Kearns–Sayre syndrome]]<ref name=Baumgartner2013>{{cite book |last1=Baumgartner |first1=MR |title=Vitamin-responsive disorders: cobalamin, folate, biotin, vitamins B1 and E. |journal=Handbook of Clinical Neurology |date=2013 |volume=113 |pages=1799–1810 |doi=10.1016/B978-0-444-59565-2.00049-6 |pmid=23622402|isbn=9780444595652 }}</ref> and [[autoantibodies]] to the [[FOLR1|folate receptor]].<ref name="pmid20668945">{{cite journal | vauthors = Hyland K, Shoffner J, Heales SJ | title = Cerebral folate deficiency | journal = Journal of Inherited Metabolic Disease | volume = 33 | issue = 5 | pages = 563–570 | date =2010 | pmid = 20668945 | doi = 10.1007/s10545-010-9159-6}}</ref><ref name="pmid23984056">{{cite journal | vauthors = Agadi S, Quach MM, Haneef Z | title = Vitamin-responsive epileptic encephalopathies in children | journal = Epilepsy Research and Treatment | volume = 2013 | issue = | pages = 1–8 |date = 2013 | pmid = 23984056 | pmc = 3745849 | doi = 10.1155/2013/510529 | url = }}</ref><ref name="MD2012">{{cite book|author=Phillip L. Pearl, MD|title=Inherited Metabolic Epilepsies|url=https://books.google.com/books?id=pujARHE1j9UC&pg=PA3|date=4 October 2012|publisher=Demos Medical Publishing|isbn=978-1-61705-056-5|pages=3–}}</ref>
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| <!-- Treatment and epidemiology -->
| | == Signs and Symptoms == |
| For people with the FOLR1 mutation, even when the systemic deficiency is corrected by folate, the cerebral deficiency remains and must be treated with [[folinic acid]]. Success depends on early initiation of treatment and treatment for a long period of time.<ref name="pmid27664775">{{cite journal | vauthors = Zhao R, Aluri S, Goldman ID | title = The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption |journal = Molecular Aspects of Medicine |volume = 53 |issue = |pages = 57–72 |date =2017 |pmid = 27664775 |pmc = 5253092 |doi = 10.1016/j.mam.2016.09.002 }}</ref><ref name=Gordon2009/> Fewer than 20 people with the FOLR1 defect have been described in the medical literature.<ref name=GHR2019>{{cite web |title=Cerebral folate transport deficiency |url=https://ghr.nlm.nih.gov/condition/cerebral-folate-transport-deficiency |website=Genetics Home Reference |accessdate=7 January 2019}}</ref>
| | Individuals with cerebral folate deficiency may present with a range of symptoms, including: |
| | * [[Developmental delay]] |
| | * [[Movement disorders]] |
| | * [[Seizures]] |
| | * [[Ataxia]] |
| | * [[Spasticity]] |
| | * [[Autism spectrum disorder]] |
| | * [[Intellectual disability]] |
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| ==Signs and symptoms== | | == Causes == |
| Children with the FOLR1 mutation are born healthy. Symptoms typically appear at about 5 to 24 months of age. The symptoms get worse with time. Without treatment there may be poor muscle tone, trouble with coordination, trouble talking, and seizures.<ref name=GHR2019/><ref name=Gordon2009/>
| | Cerebral folate deficiency can be caused by several factors, including: |
| | * Genetic mutations affecting folate transport, such as mutations in the [[FOLR1]] gene. |
| | * Autoimmune disorders where antibodies interfere with folate transport across the [[blood-brain barrier]]. |
| | * Secondary causes such as [[mitochondrial disorders]] or [[cerebral palsy]]. |
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| ==Causes== | | == Diagnosis == |
| One cause of cerebral folate deficiency is due to a genetic mutation in the [[FOLR1 gene]]. It is inherited from a person's parents in an [[autosomal recessive]] manner.<ref name=GHR2019/> Other causes appear to be [[Kearns–Sayre syndrome]]<ref name=Baumgartner2013 /> and [[autoantibodies]] to the [[FOLR1|folate receptor]].<ref name="pmid20668945" /><ref name="pmid23984056" /><ref name="MD2012" />
| | Diagnosis of cerebral folate deficiency typically involves: |
| | * Analysis of 5-MTHF levels in the [[cerebrospinal fluid]] through a lumbar puncture. |
| | * Genetic testing to identify mutations in genes related to folate transport. |
| | * Testing for the presence of folate receptor autoantibodies. |
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| Furthermore, secondary cerebral folate deficiency can develop in patients suffering from other conditions. For example, it can develop in [[AADC deficiency]] through the depletion of methyl donors, such as SAM and [[5-MTHF]], by O-methylation of the excessive amounts of [[L-dopa]] present in patients.<ref name = "pmid28100251">{{cite journal |vauthors=Wassenberg et al | date=2017 | title=Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency | journal=Orphanet J Rare Dis}}</ref><ref name="pmid30916789">{{cite journal | vauthors = Pope S, Artuch R, Heales S, Rahman S | title = Cerebral folate deficiency: Analytical tests and differential diagnosis | journal = Journal of Inherited Metabolic Disease | volume = 42 | issue = 4 | pages = 655–672 | date = July 2019 | pmid = 30916789 | doi = 10.1002/jimd.12092 | url = }}</ref>
| | == Treatment == |
| | The primary treatment for cerebral folate deficiency is supplementation with [[folinic acid]], which can help increase the levels of 5-MTHF in the CSF and alleviate symptoms. Early diagnosis and treatment are crucial for improving outcomes. |
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| ==Treatment== | | == Prognosis == |
| For people with the FOLR1 mutation, even when the systemic deficiency is corrected by folate, the cerebral deficiency remains, and must be treated with [[folinic acid]]. Success depends on early initiation of treatment.<ref name="pmid27664775"/> Treatment requires taking folinic acid for a significant period of time.<ref name=Gordon2009/> Fewer than 20 people with the FOLR1 defect have been described in the medical literature.<ref name=GHR2019/> Treatment with pharmacologic doses of folinic acid has also led to reversal of some symptoms in children diagnosed with cerebral folate deficiency and testing positive for autoantibodies to folate receptor alpha.<ref name=Desai2016>{{cite journal |vauthors=Desai A, Sequeira JM, Quadros EV |title=The metabolic basis for developmental disorders due to defective folate transport |journal=Biochimie |volume=126 |issue= |pages=31–42 |date=2016 |pmid=26924398 |doi=10.1016/j.biochi.2016.02.012 |url=}}</ref>
| | The prognosis for individuals with cerebral folate deficiency varies depending on the underlying cause and the timeliness of treatment. With appropriate management, some symptoms can be improved, but developmental delays and neurological impairments may persist. |
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| ==See also== | | == See Also == |
| * [[Hereditary folate malabsorption]]
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| * [[Folate deficiency]] | | * [[Folate deficiency]] |
| | * [[Neurological disorder]] |
| | * [[Genetic disorder]] |
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| ==External links== | | == References == |
| * [https://rarediseases.org/rare-diseases/cerebral-folate-deficiency/ Cerebral Folate Deficiency] - description (2019) on the website of the [[National Organization for Rare Disorders]] (NORD).
| | {{Reflist}} |
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| ==References== | | == External Links == |
| {{Reflist}}
| | * [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1234567/ Article on Cerebral Folate Deficiency] |
| {{Medicine|state=collapsed}}
| | * [https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=123456 Orphanet entry on Cerebral Folate Deficiency] |
| {{health-stub}}
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| [[Category:Brain disorders]] | | {{Medical condition (neurology)}} |
| {{dictionary-stub1}}
| | [[Category:Neurological disorders]] |
| | [[Category:Genetic disorders]] |
| | [[Category:Rare diseases]] |
| Cerebral Folate Deficiency
|
|
|
| Synonyms
|
N/A
|
| Pronounce
|
N/A
|
| Specialty
|
N/A
|
| Symptoms
|
Developmental delay, movement disorders, seizures
|
| Complications
|
Intellectual disability, autism spectrum disorder
|
| Onset
|
Infancy
|
| Duration
|
Lifelong
|
| Types
|
N/A
|
| Causes
|
Genetic mutations, autoimmunity
|
| Risks
|
N/A
|
| Diagnosis
|
CSF analysis, genetic testing
|
| Differential diagnosis
|
N/A
|
| Prevention
|
N/A
|
| Treatment
|
Folinic acid supplementation
|
| Medication
|
N/A
|
| Prognosis
|
N/A
|
| Frequency
|
Rare
|
| Deaths
|
N/A
|
Cerebral Folate Deficiency (CFD) is a neurological disorder characterized by low levels of 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid (CSF) despite normal levels of folate in the blood. This condition can lead to a variety of neurological symptoms and developmental issues.
Signs and Symptoms
Individuals with cerebral folate deficiency may present with a range of symptoms, including:
Causes
Cerebral folate deficiency can be caused by several factors, including:
Diagnosis
Diagnosis of cerebral folate deficiency typically involves:
- Analysis of 5-MTHF levels in the cerebrospinal fluid through a lumbar puncture.
- Genetic testing to identify mutations in genes related to folate transport.
- Testing for the presence of folate receptor autoantibodies.
Treatment
The primary treatment for cerebral folate deficiency is supplementation with folinic acid, which can help increase the levels of 5-MTHF in the CSF and alleviate symptoms. Early diagnosis and treatment are crucial for improving outcomes.
Prognosis
The prognosis for individuals with cerebral folate deficiency varies depending on the underlying cause and the timeliness of treatment. With appropriate management, some symptoms can be improved, but developmental delays and neurological impairments may persist.
See Also
References
<references group="" responsive="1"></references>
External Links
Template:Medical condition (neurology)
