For people with the FOLR1 mutation, even when the systemic deficiency is corrected by<unk> , the<unk>  deficiency remains, and must be treated with folinic acid. Folinic acid is a metabolically active form of<unk>  that can be easily introduced into the<unk>  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. Success depends on early initiation of treatment. 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. Treatment requires taking folinic acid for a significant period of time. Fewer than 20 people with the FOLR1 defect have been described in the medical literature. Treatment with pharmacologic doses of folinic acid has also led to reversal of some symptoms in children diagnosed with<unk>  and testing positive for autoantibodies to<unk>  receptor alpha. Figures == Folic acid metabolism and 5-MTHF transport across the choroid plexus epithelium in the brain. Red arrows and red crosses indicate the alternative pathway induced by FRα deficiency. Blue arrows indicate effects of folinic acid treatment. KEYS: 5-MTHF: 5-methylenetetrahydrofolate; B6: Vitamin B6; B12: Vitamin B12; CSF: cerebrospinal fluid; DHFR: dihydrofolate reductase; FRα: receptor of<unk>  alpha; Gly: glycine; GSH: glutathione reduced states; GSSG: Glutathione oxidized states; MS: methionine synthase; MTHFD: methylenetetrahydrofolate dehydrogenase; MTHFR: methylenetetrahydrofolate reductase; MTHFS: methylenetetrahydrofolate synthetase; PC: phosphatidylcholine; PCFT: proton coupled<unk>  transporter; PI: phosphatidylinositol; RFC: reduced<unk>  carrier; SAH: S-adenosyl homocysteine; SAM: S-adenosyl-methionine; Ser: Serine; SHMT: serine-hydroxy methyl transferase; SM: sphingomyelin. Figure 1 from Mafi et al., 2020.
Cerebral folate deficiency
Hereditary folate malabsorption
Vitamin E deficiency
Fluorine deficiency
Iron deficiency
Folate deficiency
Boron deficiency 
Selenium deficiency