Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter

UMMS Affiliation

Department of Pediatrics

Publication Date


Document Type



Base Sequence; DNA; Female; Flow Cytometry; Folic Acid; Genetic Variation; Humans; Immunophenotyping; Infant; Intestinal Absorption; Leucovorin; Male; Membrane Transport Proteins; *Point Mutation; Polymerase Chain Reaction; Proton-Coupled Folate Transporter; Severe Combined Immunodeficiency; T-Lymphocytes


Genetics and Genomics | Medical Genetics | Pediatrics


Hereditary folate malabsorption is a rare inborn error of metabolism due to mutations in the proton-coupled folate transporter (PCFT). Clinical presentation of PCFT deficiency may mimic severe combined immune deficiency (SCID). We report a 4-month-old female who presented with failure to thrive, normocytic anemia, Pneumocystis jirovecii pneumonia and systemic cytomegalovirus infection. Immunological evaluation revealed hypogammaglobulinemia, absent antibody responses, and lack of mitogen-induced lymphocyte proliferative responses. However, the absolute number and distribution of lymphocyte subsets, including naive T cells and recent thymic emigrants, were normal, arguing against primary SCID. Serum and cerebrospinal fluid folate levels were undetectable. A homozygous 1082-1G>A mutation of the PCFT gene was found, resulting in skipping of exon 3. Parenteral folinic acid repletion resulted in normalization of anemia, humoral and cellular immunity, and full clinical recovery. PCFT mutations should be considered in infants with SCID-like phenotype, as the immunodeficiency is reversible with parenteral folinic acid repletion.

DOI of Published Version



Clin Immunol. 2009 Dec;133(3):287-94. Epub 2009 Sep 9. Link to article on publisher's site

Journal/Book/Conference Title

Clinical immunology (Orlando, Fla.)

Related Resources

Link to Article in PubMed

PubMed ID