Immunodeficiency and inborn disorders of vitamin B12 and folate metabolism

Curr Opin Clin Nutr Metab Care. 2020 Jul;23(4):241-246. doi: 10.1097/MCO.0000000000000668.


Purpose of review: Immune dysfunction, including severe combined immunodeficiency, has been described in genetic disorders affecting the metabolism of the vitamins cobalamin (vitamin B12) and folate. We have reviewed reports of clinical findings in patients with a number of inborn errors of cobalamin or folate metabolism, specifically looking for immune problems.

Recent findings: There is little evidence that immune function is affected in most of the disorders. Exceptions are Imerslund-Gräsbeck syndrome and hereditary folate malabsorption (affecting intestinal absorption of cobalamin and folate, respectively), transcobalamin deficiency (affecting transport of cobalamin in blood and cellular cobalamin uptake), and methylenetetrahydrofolate dehydrogenase 1 deficiency (catalyzing cytoplasmic interconversion of reduced folate coenzyme derivatives).

Summary: Although some inborn errors of cobalamin or folate can be associated with immune dysfunction, the degree and type of immune dysfunction vary with no obvious pattern.

Publication types

  • Review

MeSH terms

  • Anemia, Megaloblastic / congenital
  • Anemia, Megaloblastic / immunology
  • Folic Acid / genetics
  • Folic Acid / immunology
  • Folic Acid Deficiency / congenital
  • Folic Acid Deficiency / immunology*
  • Humans
  • Malabsorption Syndromes / congenital
  • Malabsorption Syndromes / immunology*
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / deficiency
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / immunology
  • Minor Histocompatibility Antigens / immunology
  • Nutritional Physiological Phenomena / immunology*
  • Primary Immunodeficiency Diseases / immunology*
  • Proteinuria / congenital
  • Proteinuria / immunology
  • Transcobalamins / deficiency
  • Transcobalamins / immunology
  • Vitamin B 12 / genetics
  • Vitamin B 12 / immunology
  • Vitamin B 12 Deficiency / congenital
  • Vitamin B 12 Deficiency / immunology*


  • Minor Histocompatibility Antigens
  • Transcobalamins
  • Folic Acid
  • MTHFD1 protein, human
  • Methylenetetrahydrofolate Dehydrogenase (NADP)
  • Vitamin B 12

Supplementary concepts

  • Folate Malabsorption, Hereditary
  • Imerslund-Grasbeck syndrome