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

Abstract	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 naïve 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.
Authors	Arturo Borzutzky, Brian Crompton, Anke K Bergmann, Silvia Giliani, Sachin Baxi, Madelena Martin, Ellis J Neufeld, Luigi D Notarangelo
Journal	Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 133 Issue 3 Pg. 287-94 (Dec 2009) ISSN: 1521-7035 [Electronic] United States
PMID	19740703 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Membrane Transport Proteins Proton-Coupled Folate Transporter SLC46A1 protein, human DNA Folic Acid Leucovorin
Topics	Base Sequence DNA (chemistry, genetics) Female Flow Cytometry Folic Acid (blood, immunology, metabolism) Genetic Variation Humans Immunophenotyping Infant Intestinal Absorption Leucovorin (administration & dosage) Male Membrane Transport Proteins (genetics, immunology) Point Mutation Polymerase Chain Reaction Proton-Coupled Folate Transporter Severe Combined Immunodeficiency (genetics, immunology, metabolism) T-Lymphocytes (immunology)

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