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Cerebral folate transport deficiency(NCFTD)

MedGen UID:
442763
Concept ID:
C2751584
Disease or Syndrome
Synonyms: Cerebral folate deficiency syndrome; FOLATE RECEPTOR DEFICIENCY; Neurodegeneration due to cerebral folate transport deficiency; Neurodegenerative syndrome due to cerebral folate transport deficiency
SNOMED CT: Cerebral folate transport deficiency (711403001); Neurodegeneration due to cerebral folate transport deficiency (711403001); Cerebral folate deficiency (711403001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): FOLR1 (11q13.4)
 
Monarch Initiative: MONDO:0013110
OMIM®: 613068
Orphanet: ORPHA217382

Definition

NCFTD is an autosomal recessive disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy, and leukodystrophy. Recognition and diagnosis of this disorder is critical because folinic acid therapy can reverse the clinical symptoms and improve brain abnormalities and function (Steinfeld et al., 2009). [from OMIM]

Additional description

From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/cerebral-folate-transport-deficiency

Clinical features

From HPO
Neurodegeneration
MedGen UID:
17999
Concept ID:
C0027746
Cell or Molecular Dysfunction
Progressive loss of neural cells and tissue.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCerebral folate transport deficiency
Follow this link to review classifications for Cerebral folate transport deficiency in Orphanet.

Professional guidelines

PubMed

Ramaekers VT, Quadros EV
Nutrients 2022 Jul 28;14(15) doi: 10.3390/nu14153096. PMID: 35956272Free PMC Article
Frye RE, Rossignol DA, Scahill L, McDougle CJ, Huberman H, Quadros EV
Semin Pediatr Neurol 2020 Oct;35:100835. Epub 2020 Jun 25 doi: 10.1016/j.spen.2020.100835. PMID: 32892962Free PMC Article
Pope S, Artuch R, Heales S, Rahman S
J Inherit Metab Dis 2019 Jul;42(4):655-672. Epub 2019 May 2 doi: 10.1002/jimd.12092. PMID: 30916789

Recent clinical studies

Etiology

Ramaekers VT, Quadros EV
Nutrients 2022 Jul 28;14(15) doi: 10.3390/nu14153096. PMID: 35956272Free PMC Article

Diagnosis

Potic A, Perrier S, Radovic T, Gavrilovic S, Ostojic J, Tran LT, Thiffault I, Pastinen T, Schiffmann R, Bernard G
Orphanet J Rare Dis 2023 Jul 13;18(1):187. doi: 10.1186/s13023-023-02802-6. PMID: 37443037Free PMC Article
Kanmaz S, Simsek E, Yilmaz S, Durmaz A, Serin HM, Gokben S
Acta Neurol Belg 2023 Feb;123(1):121-127. Epub 2021 May 17 doi: 10.1007/s13760-021-01700-7. PMID: 34002331
Ramaekers VT, Quadros EV
Nutrients 2022 Jul 28;14(15) doi: 10.3390/nu14153096. PMID: 35956272Free PMC Article
Brunetti S, Malerba L, Giordano L, Parrini E, Guerrini R, Palumbo G, Parazzini C, Bestetti I, Accorsi P
Am J Med Genet A 2021 Aug;185(8):2526-2531. Epub 2021 May 19 doi: 10.1002/ajmg.a.62345. PMID: 34008900
Grapp M, Just IA, Linnankivi T, Wolf P, Lücke T, Häusler M, Gärtner J, Steinfeld R
Brain 2012 Jul;135(Pt 7):2022-31. Epub 2012 May 13 doi: 10.1093/brain/aws122. PMID: 22586289

Therapy

Potic A, Perrier S, Radovic T, Gavrilovic S, Ostojic J, Tran LT, Thiffault I, Pastinen T, Schiffmann R, Bernard G
Orphanet J Rare Dis 2023 Jul 13;18(1):187. doi: 10.1186/s13023-023-02802-6. PMID: 37443037Free PMC Article
Kanmaz S, Simsek E, Yilmaz S, Durmaz A, Serin HM, Gokben S
Acta Neurol Belg 2023 Feb;123(1):121-127. Epub 2021 May 17 doi: 10.1007/s13760-021-01700-7. PMID: 34002331
Ramaekers VT, Quadros EV
Nutrients 2022 Jul 28;14(15) doi: 10.3390/nu14153096. PMID: 35956272Free PMC Article
Brunetti S, Malerba L, Giordano L, Parrini E, Guerrini R, Palumbo G, Parazzini C, Bestetti I, Accorsi P
Am J Med Genet A 2021 Aug;185(8):2526-2531. Epub 2021 May 19 doi: 10.1002/ajmg.a.62345. PMID: 34008900
Zhang C, Deng X, Wen Y, He F, Yin F, Peng J
BMC Med Genet 2020 Nov 26;21(1):235. doi: 10.1186/s12881-020-01162-3. PMID: 33243190Free PMC Article

Prognosis

Potic A, Perrier S, Radovic T, Gavrilovic S, Ostojic J, Tran LT, Thiffault I, Pastinen T, Schiffmann R, Bernard G
Orphanet J Rare Dis 2023 Jul 13;18(1):187. doi: 10.1186/s13023-023-02802-6. PMID: 37443037Free PMC Article
Ramaekers VT, Quadros EV
Nutrients 2022 Jul 28;14(15) doi: 10.3390/nu14153096. PMID: 35956272Free PMC Article
Pérez-Dueñas B, Toma C, Ormazábal A, Muchart J, Sanmartí F, Bombau G, Serrano M, García-Cazorla A, Cormand B, Artuch R
J Inherit Metab Dis 2010 Dec;33(6):795-802. Epub 2010 Sep 21 doi: 10.1007/s10545-010-9196-1. PMID: 20857335

Clinical prediction guides

Chowdhury FA, Sokolov E, Anderson J, Josifova DJ, Nashef L
Pract Neurol 2024 Jan 23;24(1):56-59. doi: 10.1136/pn-2023-003727. PMID: 38135499
Pérez-Dueñas B, Toma C, Ormazábal A, Muchart J, Sanmartí F, Bombau G, Serrano M, García-Cazorla A, Cormand B, Artuch R
J Inherit Metab Dis 2010 Dec;33(6):795-802. Epub 2010 Sep 21 doi: 10.1007/s10545-010-9196-1. PMID: 20857335

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