MCID: CRB070
MIFTS: 37

Cerebral Folate Deficiency

Categories: Neuronal diseases, Rare diseases

Aliases & Classifications for Cerebral Folate Deficiency

MalaCards integrated aliases for Cerebral Folate Deficiency:

Name: Cerebral Folate Deficiency 53 25 29 6
Neurodegeneration Due to Cerebral Folate Transport Deficiency 53 25 72
Cerebral Folate Transport Deficiency 53 25
Cerebral Folate Deficiency Syndrome 53
Folr1 Deficiency 25

Classifications:



External Ids:

UMLS 72 C2751584

Summaries for Cerebral Folate Deficiency

Genetics Home Reference : 25 Cerebral folate transport deficiency is a disorder that develops from a shortage (deficiency) of the B-vitamin folate (also called vitamin B9) in the brain. Affected children have normal development during infancy, but around age 2 they begin to lose previously acquired mental and movement abilities (psychomotor regression). They develop intellectual disability, speech difficulties, and recurrent seizures (epilepsy). Movement problems such as tremors and difficulty coordinating movements (ataxia) can be severe, and some affected individuals need wheelchair assistance. Affected individuals have leukodystrophy, which is a loss of a type of brain tissue known as white matter. White matter consists of nerve fibers covered by a fatty substance called myelin that promotes the rapid transmission of nerve impulses. Leukodystrophy contributes to the neurological problems that occur in cerebral folate transport deficiency. Without treatment, these neurological problems worsen over time.

MalaCards based summary : Cerebral Folate Deficiency, also known as neurodegeneration due to cerebral folate transport deficiency, is related to neurodegeneration due to cerebral folate transport deficiency and megaloblastic anemia due to dihydrofolate reductase deficiency, and has symptoms including seizures An important gene associated with Cerebral Folate Deficiency is FOLR1 (Folate Receptor Alpha), and among its related pathways/superpathways are Selenium Micronutrient Network and One carbon pool by folate. The drugs Levoleucovorin and leucovorin have been mentioned in the context of this disorder. Affiliated tissues include brain, testes and cerebellum.

Related Diseases for Cerebral Folate Deficiency

Diseases related to Cerebral Folate Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 65)
# Related Disease Score Top Affiliating Genes
1 neurodegeneration due to cerebral folate transport deficiency 13.1
2 megaloblastic anemia due to dihydrofolate reductase deficiency 11.8
3 ataxia and polyneuropathy, adult-onset 10.3
4 mitochondrial disorders 10.3
5 kearns-sayre syndrome 10.2
6 visual epilepsy 10.2
7 seizure disorder 10.2
8 autism 10.2
9 rett syndrome 10.2
10 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.1
11 autism spectrum disorder 10.1
12 spasticity 10.1
13 basal ganglia calcification 10.1
14 leukodystrophy 10.1
15 peripheral nervous system disease 10.1
16 neuropathy 10.1
17 head injury 10.1
18 epilepsy, pyridoxine-dependent 10.0
19 aceruloplasminemia 10.0
20 sensorineural hearing loss 10.0
21 megaloblastic anemia 10.0
22 status epilepticus 10.0
23 movement disease 10.0
24 paraplegia 10.0
25 mitochondrial metabolism disease 10.0
26 slc6a3-related dopamine transporter deficiency syndrome 10.0
27 encephalopathy 10.0
28 hypotonia 10.0
29 early myoclonic encephalopathy 10.0
30 neural tube defects 9.9
31 mitochondrial dna depletion syndrome 4a 9.9
32 folate malabsorption, hereditary 9.9
33 ocular motor apraxia 9.9
34 hyperphenylalaninemia, bh4-deficient, c 9.9
35 yemenite deaf-blind hypopigmentation syndrome 9.9
36 phosphoglycerate dehydrogenase deficiency 9.9
37 branchiootic syndrome 1 9.9
38 deafness, congenital, with inner ear agenesis, microtia, and microdontia 9.9
39 alacrima, achalasia, and mental retardation syndrome 9.9
40 deficiency anemia 9.9
41 west syndrome 9.9
42 serine deficiency 9.9
43 autosomal recessive disease 9.9
44 mitochondrial dna depletion syndrome 9.9
45 spastic diplegia 9.9
46 cortical blindness 9.9
47 hepatic coma 9.9
48 hepatic encephalopathy 9.9
49 polyneuropathy 9.9
50 childhood absence epilepsy 9.9

Graphical network of the top 20 diseases related to Cerebral Folate Deficiency:



Diseases related to Cerebral Folate Deficiency

Symptoms & Phenotypes for Cerebral Folate Deficiency

UMLS symptoms related to Cerebral Folate Deficiency:


seizures

Drugs & Therapeutics for Cerebral Folate Deficiency

Drugs for Cerebral Folate Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Levoleucovorin Approved, Investigational Phase 2 68538-85-2
2
leucovorin Approved Phase 2 58-05-9 143 6006
3
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
4 Micronutrients Phase 2
5 Trace Elements Phase 2
6 Antidotes Phase 2
7 Tin Fluorides Phase 2
8 Vitamins Phase 2
9 Vitamin B9 Phase 2
10 Protective Agents Phase 2
11 Hematinics Phase 2
12 Vitamin B Complex Phase 2
13 Folate Phase 2
14 Nutrients Phase 2
15 Autoantibodies Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Folinic Acid Intervention for ASD: Links to Folate Receptor-alpha Autoimmunity & Redox Metabolism Terminated NCT01602016 Phase 2 Folinic Acid and placebo;Folinic Acid

Search NIH Clinical Center for Cerebral Folate Deficiency

Genetic Tests for Cerebral Folate Deficiency

Genetic tests related to Cerebral Folate Deficiency:

# Genetic test Affiliating Genes
1 Cerebral Folate Deficiency 29 FOLR1

Anatomical Context for Cerebral Folate Deficiency

MalaCards organs/tissues related to Cerebral Folate Deficiency:

41
Brain, Testes, Cerebellum

Publications for Cerebral Folate Deficiency

Articles related to Cerebral Folate Deficiency:

(show top 50) (show all 81)
# Title Authors PMID Year
1
Cerebral folate deficiency: Analytical tests and differential diagnosis. 38
30916789 2019
2
AP1S2-truncating variant in a patient with severe neurodevelopmental disorder and cerebral folate deficiency. 38
30383884 2019
3
Cerebral folate deficiency in adults: A heterogeneous potentially treatable condition. 38
30448717 2019
4
Complex heterozygous polymerase gamma mutation and cerebral folate deficiency in a child with refractory partial status. 38
30860128 2019
5
Cerebrospinal fluid monoamines, pterins, and folate in patients with mitochondrial diseases: systematic review and hospital experience. 38
29974349 2018
6
5,10-methenyltetrahydrofolate synthetase deficiency causes a neurometabolic disorder associated with microcephaly, epilepsy, and cerebral hypomyelination. 38
30031689 2018
7
Genetic assessment and folate receptor autoantibodies in infantile-onset cerebral folate deficiency (CFD) syndrome. 38
29661558 2018
8
Actual Insights into Treatable Inborn Errors of Metabolism Causing Epilepsy. 38
29899766 2018
9
Regulation of Reduced Folate Carrier (RFC) by Vitamin D Receptor at the Blood-Brain Barrier. 38
28885847 2017
10
Prevention of behavioral deficits in rats exposed to folate receptor antibodies: implication in autism. 38
27646260 2017
11
Identification of likely associations between cerebral folate deficiency and complex genetic- and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach. 38
28339176 2017
12
[Novel therapies in neurometabolic diseases: the importance of early intervention]. 38
28524215 2017
13
Severe leukoencephalopathy with cortical involvement and peripheral neuropathy due to FOLR1 deficiency. 38
27743887 2017
14
Folinic acid therapy in cerebral folate deficiency: marked improvement in an adult patient. 38
28054128 2017
15
The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption. 38
27664775 2017
16
Neurometabolic Disorders: Potentially Treatable Abnormalities in Patients With Treatment-Refractory Depression and Suicidal Behavior. 38
27523499 2017
17
KBG syndrome involving a single-nucleotide duplication in ANKRD11. 38
27900361 2016
18
The metabolic basis for developmental disorders due to defective folate transport. 38
26924398 2016
19
The basis for folinic acid treatment in neuro-psychiatric disorders. 38
27068282 2016
20
Teaching NeuroImages: White matter hypomyelination and progressive calcifications in cerebral folate deficiency. 38
27378809 2016
21
Epilepsy in KCNH1-related syndromes. 38
27267311 2016
22
CSF concentrations of 5-methyltetrahydrofolate in a cohort of young children with autism. 38
27178705 2016
23
Amenable Treatable Severe Pediatric Epilepsies. 38
27544473 2016
24
Late diagnosis of cerebral folate deficiency: Fewer seizures with folinic acid in adult siblings. 38
27066576 2016
25
Electrographic status epilepticus in sleep in an adult with cerebral folate deficiency. 38
26918205 2016
26
Folate receptor autoantibodies in pregnancy related complications. 38
26390016 2015
27
Can folic acid have a role in mitochondrial disorders? 38
26183769 2015
28
Total folate and 5-methyltetrahydrofolate in the cerebrospinal fluid of children: correlation and reference values. 38
25941913 2015
29
Rasmussen Syndrome and Other Inflammatory Epilepsies. 38
26060905 2015
30
CSF 5-Methyltetrahydrofolate Serial Monitoring to Guide Treatment of Congenital Folate Malabsorption Due to Proton-Coupled Folate Transporter (PCFT) Deficiency. 38
26006721 2015
31
Clinical, etiological and therapeutic aspects of cerebral folate deficiency. 38
26092490 2015
32
Follow-up of folinic acid supplementation for patients with cerebral folate deficiency and Kearns-Sayre syndrome. 38
25539952 2014
33
Diagnosis and management of cerebral folate deficiency. A form of folinic acid-responsive seizures. 38
25274592 2014
34
[Methylenetetrahydrofolate reductase deficiency-induced schizophrenia in a school-age boy]. 38
24461181 2014
35
Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors. 38
23506878 2013
36
Clinical recognition and aspects of the cerebral folate deficiency syndromes. 38
23314536 2013
37
Cerebral folate receptor autoantibodies in autism spectrum disorder. 38
22230883 2013
38
The diagnostic utility of folate receptor autoantibodies in blood. 38
23314538 2013
39
Genetic causes of cerebral folate deficiency: clinical, biochemical and therapeutic aspects. 38
22835503 2012
40
A new form of cerebral folate deficiency with severe self-injurious behaviour. 38
22861007 2012
41
[Diagnosis and treatment of cerebral folate deficiency]. 38
23302625 2012
42
Electroencephalographic and seizure manifestations in two patients with folate receptor autoimmune antibody-mediated primary cerebral folate deficiency. 38
22749608 2012
43
Cerebral folate deficiency--mishaps and misdirection. 38
22734130 2012
44
Update and new concepts in vitamin responsive disorders of folate transport and metabolism. 38
22108709 2012
45
Adult-onset cerebral folate deficiency. 38
22371854 2012
46
When do we need to perform a diagnostic lumbar puncture for neurometabolic diseases? Positive yield and retrospective analysis from a tertiary center. 38
22397043 2012
47
Cerebral folate deficiency: a neurometabolic syndrome? 38
21737328 2011
48
Pyridoxal phosphate-responsive seizures in a patient with cerebral folate deficiency (CFD) and congenital deafness with labyrinthine aplasia, microtia and microdontia (LAMM). 38
21752681 2011
49
Dihydrofolate reductase mutations-associated megaloblastic anemia and cerebral folate deficiency. 38
21388369 2011
50
Folate analysis for the differential diagnosis of profound cerebrospinal fluid folate deficiency. 38
21396357 2011

Variations for Cerebral Folate Deficiency

ClinVar genetic disease variations for Cerebral Folate Deficiency:

6 (show all 41)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 FOLR1 NM_016724.3(FOLR1): c.257G> A (p.Trp86Ter) single nucleotide variant Pathogenic rs1555069069 11:71906403-71906403 11:72195359-72195359
2 FOLR1 NM_016724.3(FOLR1): c.352C> T (p.Gln118Ter) single nucleotide variant Pathogenic rs121918405 11:71906498-71906498 11:72195454-72195454
3 FOLR1 NM_016724.3(FOLR1): c.525C> A (p.Cys175Ter) single nucleotide variant Pathogenic rs121918406 11:71906972-71906972 11:72195928-72195928
4 FOLR1 FOLR1, 18-BP DUP, NT130 duplication Pathogenic
5 FOLR1 FOLR1, SPLICE SITE MUTATION single nucleotide variant Pathogenic
6 FOLR1 NM_016724.3(FOLR1): c.493+2T> C single nucleotide variant Conflicting interpretations of pathogenicity rs144637717 11:71906793-71906793 11:72195749-72195749
7 FOLR1 NM_016724.3(FOLR1): c.261C> T (p.Asn87=) single nucleotide variant Conflicting interpretations of pathogenicity rs375444839 11:71906407-71906407 11:72195363-72195363
8 FOLR1 NM_016724.3(FOLR1): c.157T> C (p.Leu53=) single nucleotide variant Conflicting interpretations of pathogenicity rs143413500 11:71903374-71903374 11:72192330-72192330
9 FOLR1 NM_016724.3(FOLR1): c.292C> T (p.Arg98Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs76191655 11:71906438-71906438 11:72195394-72195394
10 FOLR1 NM_016724.3(FOLR1): c.103A> G (p.Asn35Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs149216939 11:71903320-71903320 11:72192276-72192276
11 FOLR1 NM_016724.3(FOLR1): c.-8-6C> T single nucleotide variant Conflicting interpretations of pathogenicity rs375060832 11:71903204-71903204 11:72192160-72192160
12 FOLR1 NM_016724.3(FOLR1): c.510A> G (p.Ala170=) single nucleotide variant Conflicting interpretations of pathogenicity rs564331848 11:71906957-71906957 11:72195913-72195913
13 FOLR1 NM_016724.3(FOLR1): c.508G> A (p.Ala170Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs139633601 11:71906955-71906955 11:72195911-72195911
14 FOLR1 NM_016724.3(FOLR1): c.588C> T (p.Ser196=) single nucleotide variant Conflicting interpretations of pathogenicity rs755278391 11:71907035-71907035 11:72195991-72195991
15 FOLR1 NM_016724.3(FOLR1): c.168+3G> A single nucleotide variant Uncertain significance rs886048642 11:71903388-71903388 11:72192344-72192344
16 FOLR1 NM_016724.3(FOLR1): c.*26_*42delinsG indel Uncertain significance rs886048643 11:71907247-71907263 11:72196203-72196219
17 FOLR1 NM_016724.3(FOLR1): c.724T> A (p.Trp242Arg) single nucleotide variant Uncertain significance rs796052445 11:71907171-71907171 11:72196127-72196127
18 FOLR1 NM_016725.2(FOLR1): c.-122C> G single nucleotide variant Uncertain significance rs886048641 11:71900690-71900690 11:72189646-72189646
19 FOLR1 NM_016724.3(FOLR1): c.13A> G (p.Met5Val) single nucleotide variant Uncertain significance rs371565364 11:71903230-71903230 11:72192186-72192186
20 FOLR1 NM_016724.3(FOLR1): c.*122A> G single nucleotide variant Uncertain significance rs886048644 11:71907343-71907343 11:72196299-72196299
21 FOLR1 NM_016724.3(FOLR1): c.623G> A (p.Arg208His) single nucleotide variant Uncertain significance 11:71907070-71907070 11:72196026-72196026
22 FOLR1 NM_016724.3(FOLR1): c.293G> A (p.Arg98Gln) single nucleotide variant Uncertain significance 11:71906439-71906439 11:72195395-72195395
23 FOLR1 NM_016724.3(FOLR1): c.451A> G (p.Thr151Ala) single nucleotide variant Uncertain significance 11:71906749-71906749 11:72195705-72195705
24 FOLR1 NM_016724.3(FOLR1): c.465_466delinsTG (p.Trp156Gly) indel Uncertain significance 11:71906763-71906764 11:72195719-72195720
25 FOLR1 NM_016724.3(FOLR1): c.71C> T (p.Thr24Ile) single nucleotide variant Uncertain significance 11:71903288-71903288 11:72192244-72192244
26 FOLR1 NM_016724.3(FOLR1): c.224A> G (p.His75Arg) single nucleotide variant Uncertain significance 11:71906370-71906370 11:72195326-72195326
27 FOLR1 NM_016724.3(FOLR1): c.322G> C (p.Glu108Gln) single nucleotide variant Uncertain significance 11:71906468-71906468 11:72195424-72195424
28 FOLR1 NM_016724.3(FOLR1): c.440G> A (p.Arg147His) single nucleotide variant Uncertain significance 11:71906738-71906738 11:72195694-72195694
29 FOLR1 NM_016724.3(FOLR1): c.503A> G (p.Lys168Arg) single nucleotide variant Uncertain significance 11:71906950-71906950 11:72195906-72195906
30 FOLR1 NM_016724.3(FOLR1): c.704G> A (p.Gly235Glu) single nucleotide variant Uncertain significance 11:71907151-71907151 11:72196107-72196107
31 FOLR1 NM_016724.3(FOLR1): c.667G> A (p.Glu223Lys) single nucleotide variant Uncertain significance 11:71907114-71907114 11:72196070-72196070
32 FOLR1 NM_016724.3(FOLR1): c.726G> A (p.Trp242Ter) single nucleotide variant Uncertain significance rs752932113 11:71907173-71907173 11:72196129-72196129
33 FOLR1 NM_016724.3(FOLR1): c.692C> T (p.Ala231Val) single nucleotide variant Uncertain significance rs1555069289 11:71907139-71907139 11:72196095-72196095
34 FOLR1 NM_016724.3(FOLR1): c.139C> G (p.Pro47Ala) single nucleotide variant Uncertain significance rs1555068662 11:71903356-71903356 11:72192312-72192312
35 FOLR1 NM_016724.3(FOLR1): c.719C> T (p.Ala240Val) single nucleotide variant Uncertain significance rs147155003 11:71907166-71907166 11:72196122-72196122
36 FOLR1 NM_016724.3(FOLR1): c.81A> C (p.Ala27=) single nucleotide variant Likely benign rs1057520285 11:71903298-71903298 11:72192254-72192254
37 FOLR1 NM_016724.3(FOLR1): c.168+8del deletion Likely benign rs762496618 11:71903393-71903393 11:72192349-72192349
38 FOLR1 NM_016724.3(FOLR1): c.393C> T (p.Asn131=) single nucleotide variant Likely benign rs61735636 11:71906691-71906691 11:72195647-72195647
39 FOLR1 NM_016724.3(FOLR1): c.642C> T (p.Phe214=) single nucleotide variant Likely benign rs868478657 11:71907089-71907089 11:72196045-72196045
40 FOLR1 NM_016724.3(FOLR1): c.169-8C> A single nucleotide variant Likely benign rs1221189280 11:71906307-71906307 11:72195263-72195263
41 FOLR1 NM_016724.3(FOLR1): c.321C> T (p.Tyr107=) single nucleotide variant Benign/Likely benign rs145674759 11:71906467-71906467 11:72195423-72195423

Expression for Cerebral Folate Deficiency

Search GEO for disease gene expression data for Cerebral Folate Deficiency.

Pathways for Cerebral Folate Deficiency

GO Terms for Cerebral Folate Deficiency

Biological processes related to Cerebral Folate Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.5 QDPR PHGDH DHFR
2 electron transport chain GO:0022900 9.26 QDPR PHGDH
3 folic acid metabolic process GO:0046655 9.16 FOLR1 DHFR
4 axon regeneration GO:0031103 8.96 FOLR1 DHFR
5 tetrahydrobiopterin biosynthetic process GO:0006729 8.62 QDPR DHFR

Molecular functions related to Cerebral Folate Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.54 QDPR PHGDH DHFR
2 electron transfer activity GO:0009055 9.32 QDPR PHGDH
3 drug binding GO:0008144 9.26 FOLR1 DHFR
4 NADPH binding GO:0070402 9.16 QDPR DHFR
5 folic acid binding GO:0005542 8.96 FOLR1 DHFR
6 methotrexate binding GO:0051870 8.62 FOLR1 DHFR

Sources for Cerebral Folate Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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