G6PC3 Deficiency

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.

Severe congenital neutropenia due to G6PC3 deficiency: Case series of five patients and literature review

“…So far, there is no evidence that G6PC3 deficiency is a preleukaemic condition. In this review, we found only 1 case of leukaemia (P70) 8 ; no other reports of malignant transformation has been described in other SCN syndromes 5,9 …”

“…Some G6PC3‐deficient patients may have a more profound immunological defect, and might require a deeper approach, including T cell flow cytometry and lymphoproliferation assays. When abnormalities in the function of T and B cells are demonstrated, it is mandatory to consider immunoglobulin replacement 9 . Progressive lymphopaenia has also been reported; therefore, immunological long‐term follow‐up is required.…”

“…In this review, we found only 1 case of leukaemia (P70) 8 ; no other reports of malignant transformation has been described in other SCN syndromes. 5,9 We have been able to include here most of the patients reported in the medical literature, expanding the phenotype and describing the typical haematological and nonhaematological features of G6PC3-deficient patients. The main limitations are the descriptive retrospective nature of the study, the fact that the information we rely upon is provided by different sources and authors, and lastly, the possibility of important data being lost throughout.…”

“…When abnormalities in the function of T and B cells are demonstrated, it is mandatory to consider immunoglobulin replacement. 9 Progressive lymphopaenia has also been reported; therefore, immunological long-term follow-up is required.…”

Severe Congenital Neutropenia Due To G6PC3 Deficiency Case Series of Five Patients and Literature Review

“…So far, there is no evidence that G6PC3 de ciency is a preleukemic condition. In this review, we found only one case of leukemia (P70) (8); no other reports of malignant transformation, as has been described in other SCN syndromes ( 5) (9). We have been able to include here most of the patients reported in the medical literature, expanding the phenotype, and describing the typical hematological and non-hematological features of G6PC3 de cient patients.…”