Diagnostic and Treatment Options for Severe IBD in Female X-CGD Carriers with Non-random X-inactivation

J Crohns Colitis. 2016 Jan;10(1):112-5. doi: 10.1093/ecco-jcc/jjv186. Epub 2015 Oct 13.


Background and aims: X-linked chronic granulomatous disease [X-CGD] due to hemizygous mutations in CYBB is characterised by invasive bacterial and fungal infections and granulomatous inflammation. Inflammatory bowel disease [IBD] is an additional or isolated manifestation. Allogeneic haematopoietic stem cell transplantation [alloHSCT] is the standard curative treatment. X-CGD carriers are usually healthy but those with non-random X-chromosome inactivation [XCI] may develop infectious or autoinflammatory manifestations.

Methods and results: We report on two female patients with severe treatment-refractory Crohn-like IBD manifesting at age 23 and 8 years, respectively. NADPH-oxidase activity testing and molecular genetics proved X-CGD carrier status with non-random XCI. As in CGD, histopathology from colonic biopsies disclosed pigment-laden macrophages and reduced CD68(+) macrophages. Following submyelo-ablative conditioning, the younger patient was treated with alloHSCT at age 20 years. She came into remission within 3 months after transplantation and shows complete mucosal healing after 16 months off all medications.

Conclusions: We suggest that children and young adults with refractory IBD should mandatorily be tested for CGD. AlloHSCT should be considered as curative therapy in severely diseased female carriers of X-CGD with non-random XCI.

Keywords: X-chromosomal chronic granulomatous disease; allogeneic haematopoietic stem cell transplantation; inflammatory bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allografts
  • Biopsy, Needle
  • Crohn Disease / genetics*
  • Crohn Disease / pathology
  • Crohn Disease / therapy*
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Granulomatous Disease, Chronic / genetics*
  • Hematopoietic Stem Cell Transplantation / methods
  • Heterozygote
  • Humans
  • Immunohistochemistry
  • Membrane Glycoproteins / genetics*
  • Mutation, Missense
  • NADPH Oxidase 2
  • NADPH Oxidases / genetics*
  • Risk Assessment
  • Sampling Studies
  • Severity of Illness Index
  • Treatment Outcome
  • X Chromosome Inactivation / genetics
  • Young Adult


  • Membrane Glycoproteins
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases