BRIEF COMMUNICATIONImpact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption

•Novel compound heterozygous SLC46A1 mutations were found in a patient with HFM.•A severe combined immunodeficiency with a T + B + NK + SCID-like phenotype was revealed.•Imbalanced serum cytokine profiles and high levels of CXCR3 ligands were disclosed.•Full recovery of the immune system after folate replacement was confirmed.•The time course of recovery varied widely among the cell types and functions.

Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder. Severe folate deficiency in HFM can result in immunodeficiency. We describe a female infant with HFM who acquired severe Pneumocystis pneumonia. The objective of the present study was to elucidate her immunological phenotype and to examine the time course of immune recovery following parenteral folate therapy. The patient demonstrated a combined immunodeficiency with an impaired T cell proliferation response, pan-hypogammaglobulinemia, and an imbalanced pro-inflammatory cytokine profile. She had normal white blood cell count, normal lymphocyte subsets, and normal complement levels. Two novel mutations were identified within the SLC46A1 gene to produce a compound heterozygote. We confirmed full recovery of her immunological and neurophysiological status with parenteral folate replacement. The time course of recovery of her immunological profile varied widely, however. HFM should be recognized as a unique form of immunodeficiency.