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

Arturo Borzutzky, Brian Crompton, Anke K. Bergmann, Silvia Giliani, Sachin Baxi, Madelena Martin, Ellis J. Neufeld, Luigi D. Notarangelo

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)287-294
Number of pages8
JournalClinical Immunology
Issue number3
StatePublished - Dec 1 2009
Externally publishedYes


  • Folic acid
  • Hereditary folate malabsorption
  • PCFT
  • Recent thymic emigrants
  • Severe combined immunodeficiency

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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