Late diagnosis of cerebral folate deficiency: Fewer seizures with folinic acid in adult siblings

  title={Late diagnosis of cerebral folate deficiency: Fewer seizures with folinic acid in adult siblings},
  author={Patrick Ferreira and Stephanie M. Luco and Sarah L. Sawyer and Jorge Davila and Kym M. Boycott and David A Dyment},
  journal={Neurology: Genetics},
Cerebral folate deficiency is a genetically heterogeneous condition.1 Mutations in FOLR1 are responsible for a rare but treatable form of cerebral folate deficiency (OMIM #613068).1 The gene codes for folate receptor alpha (FRα), a specific CNS folate transporter. Individuals with FOLR1-related folate deficiency present with ataxia, dyskinesia, spasticity, seizures, and regression in cognitive abilities and motor skills during early childhood.2 Seizures commonly observed include generalized… 

First case report of cerebral folate deficiency caused by a novel mutation of FOLR1 gene in a Chinese patient

One novel variation of FOLR1 was firstly identified from a Chinese male patient with tonic-clonic seizures, developmental delay, and ataxia, which was attributed to cerebral folate transport deficiency.

Cerebral folate deficiency in two siblings caused by biallelic variants including a novel mutation of FOLR1 gene: Intrafamilial heterogeneity following early treatment and the role of ketogenic diet

While a response to folinic acid is well established in the disorder, the efficacy of its combination with the ketogenic diet needs further evaluation, but it is suggested considering it early in the course of drug resistant epilepsy in the setting of CFD.

Cerebral folate deficiency: Analytical tests and differential diagnosis

The absorption, transport and metabolism of folate within the body; analytical methods to measure folate species in blood, plasma and CSF; inherited and acquired causes of cerebral folate deficiency; and possible treatment options in those patients found to have cerebral folates deficiency are described.

The Impact of Next-Generation Sequencing on the Diagnosis and Treatment of Epilepsy in Paediatric Patients

Next-generation sequencing has contributed to the identification of many monogenic epilepsy syndromes and is favouring earlier and more accurate diagnosis in a subset of paediatric patients with epilepsy, allowing more timely and straightforward treatment choices for specific conditions as well as avoiding needless investigations and inappropriate or unnecessary treatment choices.

Vitamins: cobalamin and folate

Folate Related Pathway Gene Analysis Reveals a Novel Metabolic Variant Associated with Alzheimer’s Disease with a Change in Metabolic Profile

An abnormal SNP in methylene tetrahydrofolate dehydrogenase 1 (MTHFD1) was significantly predictive of AD and associated with an increase in tissue glutathione and a strong prediction of susceptibility and disease among the SNPs associated with AD.

Movement Disorders in Treatable Inborn Errors of Metabolism

A general framework for a phenomenology‐based approach to movement disorders in inborn errors of metabolism is developed and an approach to identifying the “top ten” of treatable inbornerrors of metabolism that present with movement disorders is discussed—diagnoses that should never be missed.

International collaborative actions and transparency to understand, diagnose, and develop therapies for rare diseases

Critically, engagement with stakeholders from underrepresented populations and less‐developed countries must be prioritized, to enable all people living with a rare disease to receive an accurate diagnosis, care, and therapy.



Diagnosis and management of cerebral folate deficiency. A form of folinic acid-responsive seizures.

2 siblings who presented with global developmental delay and intractable seizures who responded clinically to folinic acid therapy was dramatic with improvement in social interaction, mobility, and complete seizure control.

Molecular characterization of folate receptor 1 mutations delineates cerebral folate transport deficiency.

The studies suggest that different clinical severities do not necessarily correlate with residual function of folate receptor alpha mutants and indicate that additional factors contribute to the clinical phenotype in cerebral folate transport deficiency.

Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution.

A new condition manifesting after the age of 6 months which was accompanied by low 5-MTHF in cerebrospinal fluid and responded to oral supplements with folinic acid is identified, however, the cause of disturbed folate transfer across the blood-brain barrier remains unknown.

Diagnostic utility of whole exome sequencing in patients showing cerebellar and/or vermis atrophy in childhood

The utility of whole exome sequencing for genetic diagnosis of childhood cerebellar and/or vermis atrophy is demonstrated and the main clinical features of ten patients were nonspecific and mixed.

Cerebral folate deficiency: life-changing supplementation with folinic acid.

Accepted in final form