Severe congenital neutropenia type 4 with early-onset inflammatory bowel disease attributed to a G6PC3 variant (not previously associated with disease): A case report and a literature review

Abstract

Severe congenital neutropenia type 4 is an extremely rare autosomal recessive disorder due to biallelic loss-of-function mutations affecting the glucose-6-phosphatase catalytic subunit 3 (G6PC3). It encompasses a complex heterogeneous spectrum of clinical presentations with many extra-hematological complications. In this report, we present a case of a 6-year-old Mediterranean female patient with repeated admissions due to recurrent infections, arthritis and chronic diarrhea. Thorough investigations reveled significant neutropenia, thrombocytosis, hepatosplenomegaly, delayed bone age, and Crohn's disease. Whole exome sequencing showed an extremely rare homozygous frameshift mutation affecting the penultimate exon (c.765_766del/ p.Ala257CysfsTer129); the mutation was not associated with disease previously. The patient's symptoms were controlled using antibiotics, steroids, granulocyte colony stimulating factor and infliximab. Although the latter showed marked control of both the recurrent arthritis and the inflammatory bowel disease symptoms, this was unfortunately short lived and required dose escalation and more frequent infusions.