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 journalArticle

35 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)287-294
Number of pages8
JournalClinical Immunology
Volume133
Issue number3
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

Fingerprint

Proton-Coupled Folate Transporter
Severe Combined Immunodeficiency
Phenotype
Mutation
Leucovorin
Anemia
Pneumocystis carinii
Inborn Errors Metabolism
Agammaglobulinemia
Failure to Thrive
Pneumocystis Pneumonia
Lymphocyte Subsets
Cytomegalovirus Infections
Humoral Immunity
Mitogens
Folic Acid
Cellular Immunity
Antibody Formation
Cerebrospinal Fluid
Exons

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter. / Borzutzky, Arturo; Crompton, Brian; Bergmann, Anke K.; Giliani, Silvia; Baxi, Sachin; Martin, Madelena; Neufeld, Ellis J.; Notarangelo, Luigi D.

In: Clinical Immunology, Vol. 133, No. 3, 01.12.2009, p. 287-294.

Research output: Contribution to journalArticle

Borzutzky, A, Crompton, B, Bergmann, AK, Giliani, S, Baxi, S, Martin, M, Neufeld, EJ & Notarangelo, LD 2009, 'Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter', Clinical Immunology, vol. 133, no. 3, pp. 287-294. https://doi.org/10.1016/j.clim.2009.08.006
Borzutzky, Arturo ; Crompton, Brian ; Bergmann, Anke K. ; Giliani, Silvia ; Baxi, Sachin ; Martin, Madelena ; Neufeld, Ellis J. ; Notarangelo, Luigi D. / Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter. In: Clinical Immunology. 2009 ; Vol. 133, No. 3. pp. 287-294.
@article{67311ac294814a8ca1166bb6bb3eaf82,
title = "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 na{\"i}ve 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.",
keywords = "Folic acid, Hereditary folate malabsorption, PCFT, Recent thymic emigrants, Severe combined immunodeficiency",
author = "Arturo Borzutzky and Brian Crompton and Bergmann, {Anke K.} and Silvia Giliani and Sachin Baxi and Madelena Martin and Neufeld, {Ellis J.} and Notarangelo, {Luigi D.}",
year = "2009",
month = "12",
day = "1",
doi = "10.1016/j.clim.2009.08.006",
language = "English (US)",
volume = "133",
pages = "287--294",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter

AU - Borzutzky, Arturo

AU - Crompton, Brian

AU - Bergmann, Anke K.

AU - Giliani, Silvia

AU - Baxi, Sachin

AU - Martin, Madelena

AU - Neufeld, Ellis J.

AU - Notarangelo, Luigi D.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - 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.

AB - 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.

KW - Folic acid

KW - Hereditary folate malabsorption

KW - PCFT

KW - Recent thymic emigrants

KW - Severe combined immunodeficiency

UR - http://www.scopus.com/inward/record.url?scp=70350613227&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350613227&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2009.08.006

DO - 10.1016/j.clim.2009.08.006

M3 - Article

C2 - 19740703

AN - SCOPUS:70350613227

VL - 133

SP - 287

EP - 294

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 3

ER -