title: Impact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption.
abstract: 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.
authors.affiliation: Department of Pediatrics, Sapporo Hokuyu Hospital, Higashi-Sapporo 6-6, Shiroishi-ku, Sapporo 003-0006, Japan. Electronic address: ken@yacht.ocn.ne.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kishimoto
authors.affiliation: Department of Pediatrics, Sapporo Hokuyu Hospital, Higashi-Sapporo 6-6, Shiroishi-ku, Sapporo 003-0006, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Sapporo Hokuyu Hospital, Higashi-Sapporo 6-6, Shiroishi-ku, Sapporo 003-0006, Japan.
authors.forename: Hirozumi
authors.initials: H
authors.lastname: Sano
authors.affiliation: Department of Pediatrics, Sapporo Hokuyu Hospital, Higashi-Sapporo 6-6, Shiroishi-ku, Sapporo 003-0006, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Suzuki
authors.affiliation: Department of Clinical Laboratory, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Maruoka
authors.affiliation: Department of Pediatrics, Sapporo Hokuyu Hospital, Higashi-Sapporo 6-6, Shiroishi-ku, Sapporo 003-0006, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Chida
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Pediatrics, Sapporo Hokuyu Hospital, Higashi-Sapporo 6-6, Shiroishi-ku, Sapporo 003-0006, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D001772:Blood Cell Count; D016207:Cytokines / Q000097:blood; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D005494:Folic Acid Deficiency / Q000150:complications*; D006579:Heterozygote; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D007223:Infant; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008286:Malabsorption Syndromes / Q000150:complications*; D009154:Mutation; D058979:Proton-Coupled Folate Transporter / Q000235:genetics
chemical_list: D016207:Cytokines; D007132:Immunoglobulin Isotypes; D058979:Proton-Coupled Folate Transporter; C505058:SLC46A1 protein, human; D005492:Folic Acid
keywords: Cytokine profile; Hereditary folate malabsorption; Novel mutations; Pneumocystis pneumonia; Severe combined immunodeficiency