Defects in B12 and Folate Metabolism (TCN2, SLC46A1 (PCFT Deficiency), MTHFD1)
FOCM: Folate-mediated one-carbon metabolism; HFM: Hereditary folate malabsorption; MTHFD1: Methylenetetrahydrofolate dehydrogenase 1; PCFT: Proton-coupled folate transporter; SCID: Severe combined immunodeficiency; SLC46A1: Solute carrier family 46, member 1; TCN2: Transcobalamin II
The interplay between cellular metabolism and immune function has been highlighted by the occurrence of severe combined immunodeficiency (SCID) in patients with defective mitochondrial function and purine metabolism, as reported in reticular dysgenesis, adenosine deaminase (ADA), and purine nucleoside phosphorylase (PNP) deficiency. Besides these well-established associations, only a few other metabolic defects have been reported to present with combined immunodeficiency. However, the list of metabolism-related genes causing abnormalities in the immune system is likely to grow in the coming years as a consequence of the use of next-generation sequencing technologies in patients with suspected...