Transport deficiency cerebral folate (Cerebral folate transport deficiency) - Gen FOLR1.

Transport deficiency Folate is a brain disease that develops due to a deficiency of vitamin B folate in the brain. Affected children have normal development during childhood, but about 2 years of age show a psychomotor regression. Because of this, they develop intellectual disabilities, speech difficulties and epilepsy. Movement problems such as tremors and ataxia can be serious, and some affected individuals need wheelchair. In addition, affected individuals have leukodystrophy, characterized by loss of cerebral white matter. White matter consists of nerve fibers covered by myelin which promotes rapid transmission of nerve impulses. Leukodystrophy contributes to neurological problems that occur in the brain deficiency folate transport. Without treatment, these neurological problems worsen over time.

Deficiency cerebral folate transport is due to mutations in the gene FOLR1, located on the long arm of chromosome 11 (11q13.3-Q14.1). This gene encodes a protein called alpha folate receptor. This protein helps regulate the transport of vitamin B folate cells. Folate (vitamin B9) is needed for many processes, including production and DNA repair, regulation of gene activity and protein - coding. Folate food is absorbed in the intestines and then released in a way known as 5-methyl-tetrahydrofolate (MTHF 5-) in the bloodstream, where it can be collected by the cells in various tissues. Folate receptor alpha is the inside of the cell membrane, where it binds a 5-MTHF, allowing vitamin is introduced into the cell. Folate receptor alpha is encoded in larger amounts in the brain, specifically in the choroid plexus. This region free cerebrospinal fluid, which surrounds and protects the brain and spinal cord. It is believed that the alpha folate receptor plays an important role in folate transport blood to brain cells. In the brain, folic acid is needed to produce neurotransmitters and myelin. Both substances play essential roles in signal transmission in the nervous system.

They have identified at least 11 mutations in the gene FOLR1 deficiency leading to cerebral folate transport. Most of these mutations change amino acids in the alpha folate receptor, which leads to a deficiency of protein or a protein with altered function. The absence or deficiency of folate receptor alpha in brain cells, makes 5-MTHF in the bloodstream can not be transported into the CSF and enter the brain. A folic acid deficiency in the brain affects normal, such as the production of DNA, proteins and neurotransmitters cellular functions. Folate deficiency affects the myelin stability, generating an altered production or increased degradation of the tissue, a condition known as leukodystrophy. These brain abnormalities lead to mental retardation, movement problems and epilepsy.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with cerebral deficiency of folate transport by the complete PCR amplification of exons FOLR1 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).