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., Oxford IBD cohort investigators ., Taylor JC., Taylor JM., Marsh JCW., Potter V., Travis S., Uhlig HH.

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 gene [c.911dupC; p.Q305fs*82] in an adult patient with congenital neutropenia, lymphopenia and childhood-onset, therapy-refractory Crohn's disease. Because 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.

DOI

10.1093/ecco-jcc/jjz112

Type

Journal article

Publication Date

2020-01-01T00:00:00+00:00

Volume

14

Pages

142 - 147

Total pages

5

Keywords

Exome sequencing, genomics, immunodeficiency, inflammatory bowel disease, Congenital Bone Marrow Failure Syndromes, Crohn Disease, Glycogen Storage Disease Type I, Hematopoietic Stem Cell Transplantation, Humans, Male, Neutropenia, Young Adult

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