title: Clinical profile and genetic basis of Wiskott-Aldrich syndrome at Chandigarh, North India.
abstract: BACKGROUND
  The Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency disorder characterized by thrombocytopenia with small sized platelets, eczema, and recurrent infections. There is paucity of information on WAS from the Indian subcontinent. We describe the clinical and molecular profile of 8 patients with WAS as seen in the Pediatric Immunodeficiency Clinic at the Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
  
  
  METHODS
  A detailed analysis of the clinical profiles, investigations and outcome of the 8 children diagnosed with WAS during the period 2006- 2010 was performed. Confirmation of the genetic diagnosis was done at the Service d'Hématologie, d'Immunologie et de Cytogénétique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France and the National Defense Medical College, Saitama, Japan.
  
  
  RESULTS
  8 patients were diagnosed as WAS in 5 years. The ages at diagnosis ranged from 13 weeks to 9 years while the mean age of onset of the symptoms was 117 days +/- 136 days. The diagnosis was established within a mean period of 31 months (ranging 1-108 months) from the onset of symptoms. Recurrent infections and diarrhea were seen in 6 and 7 out of the 8 patients, respectively, while eczema was variable. Autoimmunity manifestations were observed in 2 children. Thrombocytopenia and small platelet size was the hallmark of the disease and the main clinical clue to diagnosis in our patients. Mutations in the WASP gene were seen in 8 children, out of which 2 were novel mutations. While one child successfully underwent bone marrow transplantation, two children are doing well on immunoglobulin replacement and cotrimoxazole prophylaxis. Out of 8 children 4 children in our cohort died--all had high WAS scores and could not be offered hematopoietic stem cell transplantation.
  
  
  CONCLUSIONS
  WAS should be suspected clinically in any male infant with persistent unexplained thrombocytopenia and especially if the platelet size is small. Clinical presentation can be very variable and it is therefore important to recognize the entire spectrum of the disease. Understanding the molecular basis has important implications for the diagnosis, treatment, and genetic counseling of patients with WAS.
authors.affiliation: Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Suri
authors.forename: Surjit
authors.initials: S
authors.lastname: Singh
authors.forename: Amit
authors.initials: A
authors.lastname: Rawat
authors.forename: Anju
authors.initials: A
authors.lastname: Gupta
authors.forename: Chikako
authors.initials: C
authors.lastname: Kamae
authors.forename: Kenichi
authors.initials: K
authors.lastname: Honma
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Imai
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Oshima
authors.forename: Noriko
authors.initials: N
authors.lastname: Mitsuiki
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.forename: Chrystéle
authors.initials: C
authors.lastname: Bilhou-Nabera
authors.forename: Alexis
authors.initials: A
authors.lastname: Proust
authors.forename: Jasmina
authors.initials: J
authors.lastname: Ahluwalia
authors.forename: Sunil
authors.initials: S
authors.lastname: Dogra
authors.forename: Biman
authors.initials: B
authors.lastname: Saikia
authors.forename: Ranjana Walker
authors.initials: RW
authors.lastname: Minz
authors.forename: Shobha
authors.initials: S
authors.lastname: Sehgal
mesh_terms: D002648:Child; D002675:Child, Preschool; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D014923:Wiskott-Aldrich Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology