Cerebral folate transport deficiency
Cerebral folate transport deficiency is a rare genetic disorder characterized by a shortage of folate in the brain, leading to progressive neurological decline and movement difficulties.
Overview
Cerebral folate transport deficiency results from a deficiency of the B-vitamin folate (vitamin B9) within the brain. While children typically develop normally during infancy, they begin to experience psychomotor regression around age 2. Without treatment, neurological symptoms worsen over time.
Symptoms
- Psychomotor regression (loss of previously acquired mental and movement abilities)
- Intellectual disability
- Speech difficulties
- Recurrent seizures (epilepsy)
- Movement problems, including tremors and ataxia (difficulty coordinating movements)
- Leukodystrophy (loss of white matter in the brain)
Causes
The disorder is caused by mutations in the FOLR1 gene, which provides instructions for making the protein folate receptor alpha. This protein is critical for transporting folate from the bloodstream across the choroid plexus and into the cerebrospinal fluid (CSF) to reach the brain.
In the brain, folate is essential for the production of DNA, proteins, and chemical messengers called neurotransmitters. Mutations in the FOLR1 gene result in a lack of functional protein, preventing folate from entering the brain. This leads to impaired brain function and the neurological symptoms associated with the condition.
Inheritance
This condition is inherited in an autosomal recessive pattern. Both copies of the gene in each cell must have mutations for the disorder to occur. Parents of an affected individual typically carry one copy of the mutated gene without exhibiting symptoms.