Background:
Mutations in the gene Glucose-6-Phosphatase Catalytic Subunit 3 (G6PC3) result in autosomal recessive severe congenital neutropenia type 4 (SCN4) associated with multiple systems involvement such as congenital heart defects and urogenital anomalies. We recently diagnosed three patients, all sharing an identical G6PC3 mutation but differ in their clinical phenotypes.
Objective:
To provide new clinical and immunological insights regarding SCN4 and to establish diagnostic and treatment protocols.
Methods:
Three male infants first presented with recurrent infections, failure to thrive (FTT) and neutropenia underwent a thorough hematological, immunological and genetic work up. Work up included investigation of lymphocyte quantification variability and function, neutrophil function assays and bone marrow aspiration. Whole exome sequencing identified a homozygous bi-nucleotide deletion leading to frame shift mutation in G6PC3 - Del AG c.765_766, CAG->C, p.Ala257Cys. Upon diagnosis, extensive investigational survey regarding multiple systems involvement in this syndrome was held.
Results:
Clinical findings for all patients were recurrent infections, FTT and urogenital malformations. Significant lymphopenia masquerading as severe combined immunodeficiency (SCID) appeared in two patients. Patients presented with cardiac abnormalities, endocrine abnormalities and significant developmental delay. All patients responded well to Granulocyte-colony stimulating factor (G-CSF) treatment.
Conclusions:
The patients presented herein display the immunological and clinical phenotypic variability of G6PC3 deficiency. Early diagnosis and G-CSF treatment as well as prophylactic anti-microbial treatment is crucial, as well as extensive multi-system survey. Hematopoietic stem cell transplantation must be considered in case of G-CSF treatment failure.
