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Signs and Symptoms

In addition, signs of psychomotor retardation, sleep disturbances, cerebellar ataxia, and delayed development of head growth can occur. At around age three, visual disturbances can develop, and sensorineural hearing loss can occur at around age six. In children with cerebral folate deficiency, the cerebrospinal fluid shows low levels of 5MTHF, and a loss of white matter in the brain (leukodystrophy) may occur. As a result of the decreased levels of 5MTHF, the child experiences low levels of Vitamin B folate. There is inability for the 5MTHF to be transported across the blood-brain barrier, resulting in symptoms of seizures, delayed cognitive and motor processing, and autistic features.

Causes

The mutation of the FOLR1 gene causes an inability to produce the FRA protein. More commonly, CFD involves the malfunction and disruption of the folate receptor alpha (FRA). One way the FRA can be disrupted is by the attachment of the autoantibodies, causing dysfunction in the receptor. Also, a mitochondrial disease can impact the functioning of the folate receptor alpha. In order for the receptor to function properly, energy from the mitochondria is required. Folate must be actively transported into the brain, so ATP from the mitochondria is essential. If the individual has a mitochondrial disease, the FRA could be lacking adequate energy, resulting in the deficiency of folate in the brain.

Treatment

Folinic acid is a metabolically active form of folate that can be easily introduced into the folate cycle. A typical dose that is administered to children is 0.5-1 mg/kg daily, but the dose can be increased depending on the severity of symptoms and the age of the child. Over time, the treatment with folinic acid has shown to reduce a variety of symptoms of CFD. The treatment of folinic acid can lead to improvements in walking, speech, interpersonal skills and reduction in seizures. The improvements vary depending on the age that the treatment was first given. Starting the folinic acid treatment before the age of six is more advantageous for the child with CFD. If the treatment is started after the age of six, its results are not as effective.