Referral network in Asia: Database review 2001-2009

Free Paper Oral presentation: FREE PAPER 17: FP17-01OBJECTIVES: Primary immunodeficiency disorders (PIDs) are inborn errors of the immune system. Because of their rarity, multi-center collaboration for pooled data analysis and molecular studies is important to gain meaningful insights about the phenotypic and genetic diversities of PIDs. Since 2001, our unit established collaboration with more than 20 pediatric centers in China and Southeast Asia. It is imperative to organize the data systematically to yield information on epidemiology of PIDs in this region. METHODS: In 2009, a web-based PID patient database was established by HKU, and a full database review was performed. The password-protected database contains clinical and mutation data of patients referred to our unit for genetic diagnosis. All referring doctors have access to information of patients under their care. A web-based referral system was incorporated, where referring doctors can make requests for genetic tests and provide clinical data in a standardized format. Appropriate genetic tests will be performed after detailed discussion, based on patient’s clinical and immunological phenotype. MAIN RESULTS: 619 entries were recorded, including 344 genetic tests performed on 289 patients and 275 carrier screening. Eighty-nine patients (30.8%) were from Hong Kong, 150 (51.9%) were from mainland China while the rest were from Taiwan, Singapore, Malaysia, Thailand, the Philipines and Australia. Mutations in PID genes were confirmed in 176 patients, and 157 carriers were identified. X-linked agammaglobulinemia (n=69), Wiskott-Aldrich syndrome (n=36), X-linked chronic granulomatous disease (CGD, n=22), X-linked hyperIgM (n=15) and X-linked severe combined immunodeficiency (SCID, n=13) constituted majority of cases. We also identified mutations of rare PIDs, such as autosomal-recessive SCID (IL7R, JAK3, RAG2 and DCLRE1C), autosomal-recessive CGD (NCF1, CYBA), defects of IL12/IFN-gamma axis in patients susceptible to mycobacterial infections, FOXP3 mutation in immunodysregulation-polyendocrinopathy-X-linked (IPEX) syndrome, SH2D1A mutations in X-linked lymphoproliferative syndrome, and ITGB2 mutations in leucocyte adhesion deficiency. However, mutations could not be identified in 40% of patients despite distinct clinical and immunological phenotypes. Overall, children with PIDs were diagnosed at a much earlier age in the recent years, but in China many patients with life-threatening PIDs died very young because of limited access to transplant service. CONCLUSION: Establishment of PID database and referral network is an initial step to multi-center collaboration. This constitutes the foundation for PID research and documentation of prevalence, disease burden and outcome of patients with PIDs. Currently we offer genetic tests on 50 PID genes, and more are under development. New genetic technology, such as microarray and exome sequencing will enable efficient ways of molecular diagnosis.The 6th Congress of Asian Society for Pediatric Research & 51st Annual Meeting of Taiwan Pediatric Association, Taipei, Taiwan, 15-18 April 201