title: G6PC3 Deficiency: Primary Immune Deficiency Beyond Just Neutropenia.
abstract: Glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency was recently defined as a new severe congenital neutropenia subgroup remarkable with congenital heart defects, urogenital malformations, endocrine abnormalities, and prominent superficial veins. Here, we report 3 patients with G6PC3 deficiency presenting with recurrent diarrhea, failure to thrive, and sinopulmonary infections leading to bronchiectasis. In patient I and II, a combined immune deficiency was suspected due to early-onset disease with lymphopenia, neutropenia, and thrombocytopenia, along with variable reductions in lymphocyte subpopulations and favorable response to intravenous γ-globulin therapy. Apart from neutropenia, all 3 patients had intermittent thrombocytopenia, anemia, and lymphopenia. All patients had failure to thrive and some of the classic syndromic features of G6PC3 deficiency, including cardiac abnormalities and visibility of superficial veins in all, endocrinologic problems in PI and PIII, and urogenital abnormalities in PII. Our experience suggests that a diagnosis of congenital neutropenia due to G6PC3 may not be as straightforward in such patients with combined lymphopenia and thrombocytopenia. A high index of suspicion and the other syndromic features of G6PC3 were clues to diagnosis. Screening of all combined immune deficiencies with neutropenia may help to uncover the whole spectra of G6PC3 deficiency.
authors.affiliation: *Division of Pediatric Allergy and Immunology †Department of Pathology, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey ‡CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences §Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Ayca
authors.initials: A
authors.lastname: Kiykim
authors.forename: Safa
authors.initials: S
authors.lastname: Baris
authors.forename: Elif
authors.initials: E
authors.lastname: Karakoc-Aydiner
authors.forename: Ahmet O
authors.initials: AO
authors.lastname: Ozen
authors.forename: Ismail
authors.initials: I
authors.lastname: Ogulur
authors.forename: Suheyla
authors.initials: S
authors.lastname: Bozkurt
authors.forename: Cigdem C
authors.initials: CC
authors.lastname: Ataizi
authors.forename: Kaan
authors.initials: K
authors.lastname: Boztug
authors.forename: Isil B
authors.initials: IB
authors.lastname: Barlan
mesh_terms: D000015:Abnormalities, Multiple / Q000201:enzymology / Q000235:genetics*; D000293:Adolescent; D001987:Bronchiectasis / Q000209:etiology; D020134:Catalytic Domain; D019070:Cell Lineage; D002648:Child; D018389:Codon, Nonsense; D003092:Colitis / Q000201:enzymology / Q000235:genetics; D003241:Consanguinity; D003967:Diarrhea / Q000201:enzymology / Q000235:genetics; D005091:Exons / Q000235:genetics; D005183:Failure to Thrive / Q000201:enzymology / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D005953:Glycogen Storage Disease Type I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics*; D016131:Lymphocyte Subsets / Q000473:pathology*; D008231:Lymphopenia / Q000151:congenital / Q000201:enzymology / Q000235:genetics; D008297:Male; D016254:Mutagenesis, Insertional; D009503:Neutropenia / Q000201:enzymology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics; D012141:Respiratory Tract Infections / Q000150:complications; D013921:Thrombocytopenia / Q000151:congenital / Q000201:enzymology / Q000235:genetics; D014421:Turkey
chemical_list: D018389:Codon, Nonsense; D022821:RNA Splice Sites; D005952:Glucose-6-Phosphatase; C492193:G6PC3 protein, human