Journal of Inherited Metabolic Disease

, Volume 35, Issue 4, pp 665–670 | Cite as

Update and new concepts in vitamin responsive disorders of folate transport and metabolism

SSIEM Symposium 2011


Derivatives of folic acid are involved in transfer of one-carbon units in cellular metabolism, playing a role in synthesis of purines and thymidylate and in the remethylation of homocysteine to form methionine. Five inborn errors affecting folate transport and metabolism have been well studied: hereditary folate malabsorption, caused by mutations in the gene encoding the proton-coupled folate transporter (SLC46A1); glutamate formiminotransferase deficiency, caused by mutations in the FTCD gene; methylenetetrahydrofolate reductase deficiency, caused by mutations in the MTHFR gene; and functional methionine synthase deficiency, either as the result of mutations affecting methionine synthase itself (cblG, caused by mutations in the MTR gene) or affecting the accessory protein methionine synthase reductase (cblE, caused by mutations in the MTRR gene). Recently additional inborn errors have been identified. Cerebral folate deficiency is a clinically heterogeneous disorder, which in a few families is caused by mutations in the FOLR1 gene. Dihydrofolate reductase deficiency is characterized by megaloblastic anemia and cerebral folate deficiency, with variable neurological findings. It is caused by mutations in the DHFR gene. Deficiency in the trifunctional enzyme containing methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase and formyltetrahydrofolate synthetase activities, has been identified in a single patient with megaloblastic anemia, atypical hemolytic uremic syndrome and severe combined immune deficiency. It is caused by mutations in the MTHFD1 gene.


Folate Homocysteine Folate Receptor Megaloblastic Anemia Reduce Folate Carrier 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Dihydrofolate reductase






Folate receptors alpha and beta








Methylenetetrahydrofolate reductase


Proton-coupled folate transporter


Reduced folate carrier




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Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  1. 1.The Hess B and Diane Finestone Laboratory in Memory of Jacob and Jenny Finestone, and Department of Human GeneticsMcGill University Health CentreMontrealCanada

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