Asian Society for Pediatric Research (ASPR) and the Perinatal Society of Malaysia (PSM).
Abstract
Conference Theme: Inflammatory Basis of Perinatal and Childhood DiseasesSymposium 40: InfectionBackground: Chronic granulomatous disease (CGD) is a phagocytic disorder
caused by defective NADPH oxidase activity. Affected individuals are susceptible
to bacterial infections, mycosis and hyperinflammatory complications. Variations
in the epidemiology of infectious diseases across geographical regions can lead
to distinct clinical phenotypes.
Objective: To identify the unique clinical characteristics of a large cohort of CGD
patients in China and Southeast Asia referred for genetic studies from 2003 to
2012.
Methods: 53 patients with genetically-confirmed CGD were included and their
clinical features were analyzed. CYBB and CYBA mutations were studied by
Sanger sequencing, and NCF1 ‘GT’ deletion hotspot mutation was studied on
genomic DNA by GeneScan.
Results: 44 patients with X-CGD had CYBB mutations (missense[n=16];
nonsense[n=8]; deletion[n=9]; insertion[n=2]; intron mutation[n=9]). Nine
patient had AR-CGD (CYBA[n=5]; NCF1 75_76delGT[n=4]). The median age at
presentation and diagnosis was higher in AR-CGD (7m and 66m) compared with
X-CGD (3m and 22m). The commonest presentations were pneumonia (58%), skin and perianal abscess (49%), lymphadenitis (42%) and recurrent diarrhea (30%).
Aspergillosis and salmonellosis occurred at a frequency similar to published
studies (13% and 19% respectively), but the commonest infection was BCG (43%)
and 11% had disseminated BCG. 21% of patients had tuberculosis. Fulminant
melioidosis and Chromobacterium violaceum infections occurred in 3 patients
and two of their male siblings. Hyperinflammatory conditions included polyarthritis
(n=3) and pulmonary granuloma (n=2). Death was recorded in 8 patients (15%).
Conclusion: Melioidosis and C. violaceum indigenous to Southeast Asia can cause
life-threatening infections in CGD patients. The high incidence of mycobacterial
infections is associated with universal BCG vaccination and endemicity of
tuberculosis. Such observations emphasize the role of respiratory burst as an
immune defense mechanism against these pathogens. These infections are
seldom reported in Caucasian cohorts, illustrating the importance of regional
collaborative studies to facilitate pattern recognition and early diagnosis of
primary immunodeficiencies.published_or_final_versio
