Cerebral folate transport deficiency

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Reviewed September 2014

What is cerebral folate transport deficiency?

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.

How common is cerebral folate transport deficiency?

The prevalence of cerebral folate transport deficiency is unknown. Fewer than 20 affected individuals have been described in the scientific literature.

What genes are related to cerebral folate transport deficiency?

Mutations in the FOLR1 gene cause cerebral folate transport deficiency. The FOLR1 gene provides instructions for making a protein called folate receptor alpha. This protein is found within the cell membrane where it attaches (binds) to folate, allowing the vitamin to be brought into the cell. Folate receptor alpha is produced in largest amounts in the brain, specifically in an area of the brain called the choroid plexus. This region releases cerebrospinal fluid (CSF), which surrounds and protects the brain and spinal cord. Folate receptor alpha is thought to play a major role in bringing folate from the bloodstream into brain cells. It transports folate across the choroid plexus and into the CSF, ultimately reaching the brain. In the brain, folate is needed for making myelin and chemical messengers called neurotransmitters. Both of these substances play essential roles in transmitting signals in the nervous system. Additionally, folate is involved in the production and repair of DNA, regulation of gene activity (expression), and protein production.

FOLR1 gene mutations result in a lack of protein or malfunctioning protein. As a result, folate from the bloodstream cannot be transported into the CSF. Without folate, many processes in the brain are impaired, leading to the neurological problems typical of cerebral folate transport deficiency.

The signs and symptoms of cerebral folate transport deficiency do not begin until late infancy because other mechanisms can compensate for this loss. For example, another protein called folate receptor beta is responsible for folate transport before birth and in early infancy.

How do people inherit cerebral folate transport deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of cerebral folate transport deficiency?

These resources address the diagnosis or management of cerebral folate transport deficiency and may include treatment providers.

You might also find information on the diagnosis or management of cerebral folate transport deficiency in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about cerebral folate transport deficiency?

You may find the following resources about cerebral folate transport deficiency helpful. These materials are written for the general public.

MedlinePlus - Health information (6 links)
Additional NIH Resources - National Institutes of Health (2 links)
Educational resources - Information pages (10 links)
Patient support - For patients and families (5 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information (1 link)
OMIM - Genetic disorder catalog

What other names do people use for cerebral folate transport deficiency?

cerebral folate deficiency
FOLR1 deficiency
neurodegeneration due to cerebral folate transport deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about cerebral folate transport deficiency?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding cerebral folate transport deficiency?

ataxia ; autosomal ; autosomal recessive ; cell ; cell membrane ; choroid ; choroid plexus ;deficiency ; disability ; DNA ; endocytosis ; epilepsy ; folate ; gene ; inherited ; leukodystrophy ;metabolism ; methyl ; nervous system ; neurological ; neurotransmitters ; prevalence ; protein ;psychomotor ; receptor ; recessive ; regression ; tissue ; white matter

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (8 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.