title: Diagnostic and Treatment Options for Severe IBD in Female X-CGD Carriers with Non-random X-inactivation.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Pediatric Hematology/Oncology/Immunology/Stem Cell Transplantation, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany Immunological Diagnostics Laboratory, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany fabian.hauck@med.uni-muenchen.de.
authors.forename: Fabian
authors.initials: F
authors.lastname: Hauck
authors.affiliation: Pediatric Gastroenterology/Hepatology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Koletzko
authors.affiliation: Institute of Pathology, Ludwig-Maximilians University of Munich, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Walz
authors.affiliation: Pediatric Pneumology and Immunology, Charité University Medicine, Berlin, Germany Labor Berlin, Immunology, Charité and Vivantes GmbH, Berlin, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: von Bernuth
authors.affiliation: Pediatric Hematology/Oncology/Immunology/Stem Cell Transplantation, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Klenk
authors.affiliation: Pediatric Hematology/Oncology/Immunology/Stem Cell Transplantation, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Schmid
authors.affiliation: Pediatric Hematology/Oncology/Immunology/Stem Cell Transplantation, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Belohradsky
authors.affiliation: Pediatric Hematology/Oncology/Immunology/Stem Cell Transplantation, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Klein
authors.affiliation: Pediatric Gastroenterology/Hepatology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Bufler
authors.affiliation: Pediatric Hematology/Oncology/Immunology/Stem Cell Transplantation, Dr von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Albert
mesh_terms: D000328:Adult; D064591:Allografts; D001707:Biopsy, Needle; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics*; D020125:Mutation, Missense; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D018570:Risk Assessment; D012494:Sampling Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D049951:X Chromosome Inactivation / Q000235:genetics; D055815:Young Adult
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: X-chromosomal chronic granulomatous disease; allogeneic haematopoietic stem cell transplantation; inflammatory bowel disease