title: Clinical, immunological, and molecular characterization of hyper-IgM syndrome due to CD40 deficiency in eleven patients.
abstract: OBJECTIVE
  Hyper-IgM syndrome due to CD40 deficiency (HIGM3) is a rare form of primary immunodeficiency with few reported cases. In this study, we further characterize the clinical, immunological, and molecular profiles of the disease in a cohort of 11 patients.
  
  
  METHODS
  Molecular genetic analysis and a comprehensive clinical review of patients diagnosed with HIGM3 at our tertiary care center from 1994 to 2011 were undertaken.
  
  
  RESULTS
  Eleven patients from seven families were enrolled. The patients had a median age of 9 years [ranging from 2 to 22 years old]. All 11 patients had recurrent chest infections at presentation. Pneumocystis jiroveci pneumonia was confirmed in three patients. Five patients had sclerosing cholangitis, and five patients had Cryptosporidium isolated from their stool. Six patients had nasal and sinus infections, and two of these patients had destructive nasal fungal infections. Eight patients had neutropenia. All of the patients had low IgG and normal or high IgM levels. IgA was undetectable in all but three patients. Two novel mutations were found: a splice site for intron 3 and a missense mutation located in the coding region of exon 3. Two patients underwent successful stem cell transplantation from a matched donor. Four patients are doing well on prophylaxis; two are very sick, one with protracted diarrhea and persistent Cryptosporidium and the other with neurological complications. Three patients died early in life as a result of severe sepsis.
  
  
  CONCLUSIONS
  To our knowledge, this report provides the largest cohort of patients with this disease with a very long follow-up period. Our cohort showed variable disease severity
authors.forename: Bandar K
authors.initials: BK
authors.lastname: Al-Saud
authors.forename: Zobaida
authors.initials: Z
authors.lastname: Al-Sum
authors.forename: Hanadi
authors.initials: H
authors.lastname: Alassiri
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Al-Ghonaium
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.forename: Hasan
authors.initials: H
authors.lastname: Al-Dhekri
authors.forename: Rand
authors.initials: R
authors.lastname: Arnaout
authors.forename: Osama
authors.initials: O
authors.lastname: Alsmadi
authors.forename: Esteban
authors.initials: E
authors.lastname: Borrero
authors.forename: Asm'a
authors.initials: A
authors.lastname: Abu-Staiteh
authors.forename: Faisal
authors.initials: F
authors.lastname: Rawas
authors.forename: Hamoud
authors.initials: H
authors.lastname: Al-Mousa
authors.forename: Abbas
authors.initials: A
authors.lastname: Hawwari
mesh_terms: D000293:Adolescent; D019013:CD40 Antigens / Q000172:deficiency* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D007223:Infant; D008297:Male; D009154:Mutation; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019013:CD40 Antigens