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cerebral folate receptor alpha deficiency
ICD-10 Codes
Related ICD-10:
Description
Cerebral Folate Receptor Alpha Deficiency: A Treatable Neurodegenerative Disorder
Cerebral folate receptor alpha (FRα) deficiency is a rare neurodevelopmental disorder caused by a shortage of the B-vitamin folate in the brain. This condition affects the transport of 5-methyltetrahydrofolate (5-MTHF), a crucial form of folate, into the brain.
Signs and Symptoms
The symptoms of cerebral folate receptor alpha deficiency can vary from person to person but often include:
- Movement disturbances
- Loss of previously acquired mental and movement abilities
- Poor muscle control (ataxia)
- Epilepsy
- Irritability and anxiety
- Poor sleep
- Gross motor problems or coordination issues
- Tics
- Seizures, including absence seizures, myoclonic fits, and tonic-clonic episodes
Causes and Diagnosis
Cerebral folate receptor alpha deficiency is caused by a defect in the folate receptor alpha gene, leading to impaired transport of 5-MTHF into the brain. This condition can be diagnosed through various tests, including:
- Measurement of 5-MTHF levels in cerebral spinal fluid
- Genetic testing for mutations in the folate receptor alpha gene
Treatment and Management
Fortunately, cerebral folate receptor alpha deficiency is a treatable condition. Treatment typically involves supplementation with 5-MTHF, which can help alleviate symptoms and improve cognitive and motor function.
References
- [1] 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. [2]
- The cerebral folate receptor alpha (FRα) transports 5-methyltetrahydrofolate (5-MTHF) into the brain; low 5-MTHF in the brain causes cerebral folate deficiency. [3]
- Folate receptor alpha defect causes cerebral folate transport deficiency: a treatable neurodegenerative disorder associated with disturbed myelin metabolism. [5]
- Symptoms range from sleep disturbance, irritability, visual disturbance and seizures in the form of absence seizure, myoclonic fits and tonic-clonic episodes. [6]
Additional Characteristics
- Tics
- Epilepsy
- Movement disturbances
- Loss of previously acquired mental and movement abilities
- Poor muscle control (ataxia)
- Irritability and anxiety
- Poor sleep
- Gross motor problems or coordination issues
- Seizures, including absence seizures, myoclonic fits, and tonic-clonic episodes
Signs and Symptoms
Early symptoms of cerebral folate receptor alpha deficiency include intellectual disability, speech difficulties, and recurrent seizures in a third of affected children [1].
Some common signs and symptoms of this condition are:
- Intellectual disability: Individuals with cerebral folate receptor alpha deficiency may experience significant delays or regression in their cognitive development [4].
- Speech difficulties: Speech problems, including trouble talking, are also a characteristic feature of this condition [6].
- Recurrent seizures (epilepsy): Seizures occur in approximately one-third of affected children and can be a recurring issue [1][2].
- Movement disturbances: Movement problems such as tremors, difficulty with coordination, and poor muscle control (ataxia) are also associated with cerebral folate receptor alpha deficiency [4].
- Developmental delay or regression: Some individuals may experience delays or regression in their developmental milestones [5].
Without treatment, additional symptoms can include poor muscle tone, trouble with coordination, and seizures [6].
It's essential to note that these symptoms can vary in severity and presentation among affected individuals.
Additional Symptoms
- Intellectual disability
- Speech difficulties
- Developmental delay or regression
- Movement disturbances
- Recurrent seizures
- Poor muscle tone
- Trouble with coordination
Diagnostic Tests
Diagnostic Tests for Cerebral Folate Receptor Alpha Deficiency
Cerebral folate receptor alpha (CFRA) deficiency, also known as cerebral folate deficiency (CFD), is a rare disorder that affects the brain's ability to absorb folate. Diagnostic tests are essential to confirm this condition.
- Molecular Genetic Testing: This test identifies biallelic FOLR1 pathogenic variants in individuals with CFRA deficiency [1].
- Blood Test: A blood test can determine if an individual has Foliate Receptor Autoantibodies (FRAAs), which are associated with CFD [4]. However, this test cannot confirm the presence of CFRA deficiency.
- Cerebrospinal Fluid (CSF) Analysis: This procedure involves taking a sample of CSF from the brain and spinal cord to detect autoantibodies that interfere with folate transfer [8].
- Imaging Studies: MRI brain scans may show delayed myelination and demyelinated subcortical and periventricular areas in individuals with untreated CFD [3].
References:
[1] Jan 11, 2024 — The diagnosis of FOLR1-CFTD is established in a proband with biallelic FOLR1 pathogenic variants identified by molecular genetic testing. [3] by VT Ramaekers · 2022 · Cited by 32 — Among half of the untreated CFD cases, MRI brain scans show delayed myelination with demyelinated subcortical and periventricular areas, ... [4] A blood test can determine if your child has FRAAs. It is important to note that a Folate Receptor Autoantibody Test cannot tell you whether or not your child ... [8] by VT Ramaekers · 2005 · Cited by 293 — Cerebral folate deficiency is a disorder in which autoantibodies can prevent the transfer of folate from the plasma to the cerebrospinal fluid.
Additional Diagnostic Tests
- Blood Test
- Imaging Studies
- Cerebrospinal Fluid (CSF) Analysis
- Molecular Genetic Testing
Treatment
Cerebral folate receptor alpha (FRα) deficiency can be treated with various medications, including:
- d,l-leucovorin (folinic acid): This is a form of folic acid that can be used to treat FRα deficiency. It works by bypassing the defective FRα protein and directly delivering folate into the brain [3][6].
- High-dose methyfolate: This medication has been shown to be beneficial in treating FRα deficiency, particularly in children with autism spectrum disorders (ASD) [4][8].
- Folinic acid supplementation: Daily administration of high-dose folinic acid has been found to be effective in controlling symptoms and improving cognitive function in individuals with FRα deficiency [7].
It's essential to note that these treatments may have varying degrees of success, and individual results may differ. A healthcare professional should be consulted for personalized guidance on medication treatment.
References:
[3] Rossignol DA (2021) - CFD has been associated with autism spectrum disorders (ASD) and is treated with d,l-leucovorin (folinic acid).
[6] Oct 15, 2022 - Folinic acid (tradename Leucovorin) is a form of folic acid that can be used to treat cerebral folate deficiency.
[7] Ramaekers VT (2014) - Daily administration of high-dose folinic acid appears to be beneficial for the control of negative and positive symptoms.
[8] Frye RE (2013) - This study suggests that FRAs may be important in ASD and that FRA-positive children with ASD may benefit from leucovorin calcium treatment.
Recommended Medications
- acid
- High-dose methyfolate
💊 Drug information is sourced from ChEBI (Chemical Entities of Biological Interest) database. Always consult with a healthcare professional before starting any medication. Click on any medication name for detailed information.
Differential Diagnosis
Additional Differential Diagnoses
- item2
- item3
- item1
Additional Information
- core#notation
- DOID:0050719
- rdf-schema#label
- cerebral folate receptor alpha deficiency
- rdf-schema#subClassOf
- t332329
- 22-rdf-syntax-ns#type
- http://www.w3.org/2002/07/owl#Class
- rdf-schema#domain
- https://w3id.org/def/predibionto#has_symptom_755
- owl#annotatedSource
- t332497
- oboInOwl#hasOBONamespace
- disease_ontology
- oboInOwl#created_by
- lschriml
- oboInOwl#creation_date
- 2012-06-11T02:58:59Z
- oboInOwl#id
- DOID:0050719
- oboInOwl#hasDbXref
- MIM:613068
- oboInOwl#hasExactSynonym
- Neurodegeneration due to cerebral folate transport deficiency
- IAO_0000115
- A vitamin metabolic disorder that has_material_basis_in mutations in the folate receptor 1 (FOLR1) gene coding for folate receptor alpha (FRalpha), is located_in the brain and is characterized by progressive movement disturbance, psychomotor decline, and epilepsy.
- IDO_0000664
- http://purl.obolibrary.org/obo/GENO_0000148
- RO_0004026
- http://purl.obolibrary.org/obo/UBERON_0001893
- relatedICD
- http://example.org/icd10/E75.243
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