Because HFM is a rare disorder, there are no studies that define its optimal treatment. Correction of the systemic folate deficiency, with the normalization of folate blood levels, is easily achieved with high doses of oral folates or much smaller doses of parenteral folate. This will rapidly correct the anemia, immune deficiency and GI signs. The challenge is to achieve adequate treatment of the neurological component of HFM. It is essential that the folate dose is sufficiently high to achieve CSF folate levels as close as possible to the normal range for the age of the child. This requires close monitoring of the CSF folate level. The physiological folate is 5-methyltetrahydrofolate but the oral formulation available is insufficient for treatment of this disorder and a parenteral form is not available. The optimal folate at this time is 5-formyltetrahydrofolate which, after administration, is converted to 5-methyltetrahydrofolate. The racemic mixture of 5-formyltetrahydrofolate (leucovorin) is generally available; the active S-isomer, levoleucovorin, may be obtained as well. Parenteral administration is the optimal treatment if that is possible. Folic acid should not be used for the treatment of HFM. Folic acid is not a physiological folate. It binds tightly to, and may impede, FRα-mediated endocytosis which plays an important role in the transport of folates across the choroid plexus into the CSF (see above). For a further consideration of treatment see GeneReviews.
Hereditary folate malabsorption
Cerebral folate deficiency
Folate deficiency
Iron metabolism disorder
Iron deficiency
Zinc deficiency
Vitamin E deficiency
Familial isolated vitamin E deficiency