Remission of inflammatory bowel disease in Glucose-6-Phosphatase 3 deficiency by allogeneic haematopoietic stem cell transplantation.
Bolton C., Burch N., Morgan J., Harrison B., Pandey S., Pagnamenta AT., Taylor JC., Taylor JM., Marsh JCW., Potter V., Travis S., Uhlig HH., Oxford IBD cohort investigators None.
Mendelian disorders in glucose-6-phosphate metabolism can present with inflammatory bowel disease (IBD). Using whole genome sequencing we identified a homozygous variant in the glucose-6-phosphatase G6PC3 (c.911dupC; p.Q305fs*82) in an adult patient with congenital neutropenia, lymphopenia and childhood-onset, therapy-refractory Crohn's disease. Since G6PC3 is expressed in several haematopoietic and non-haematopoietic cells it was unclear whether allogeneic stem cell transplantation (HSCT) would benefit this patient with intestinal inflammation. We show that HSCT resolves G6PC3-associated immunodeficiency and the Crohn's disease phenotype. It illustrates how even in adulthood, next generation sequencing can have a significant impact on clinical practice and healthcare utilization in patients with immunodeficiency and monogenic IBD.