Abstract
BackgroundChronic granulomatous disease (CGD) is a rare primary immunodeficiency of the phagocytic cells, which results in absent or diminished levels of microbicidal reactive oxygen species. The disease occurs due to germline mutations in the genes encoding the five subunits of NADPH oxidase complex. The present study is a pilot study to understand the clinical and genetic aspects of CGD in Sri Lanka.MethodsClinical records of thirteen CGD patients were analysed and compared with similar studies performed in different countries and regions to identify patterns in demographics, clinical manifestations and infectious agents. Genomic DNA and cDNA were analysed in eight patients to identify mutations in CYBB and NCF1 genes, thereby to ascertain the potential X-linked and autosomal recessive (AR) CGD patients.ResultsThe onset of symptoms in the patient cohort was very early (mean 4.6 months) compared to 20 months in India and 23.9 months in Latin America. Similarly, the age at diagnosis was lower (mean 1.6 years after birth) compared to other studies; 4.5 years in India and 6.1 years in Europe. Pulmonary manifestations were the most common (85%), followed by skin/subcutaneous infections (77%) and lymphadenopathy (62%). The death rate of local patients (38%) was higher than other countries (India 35%, Europe 20%). Majority (77%) were treated for tuberculosis at some point in life. Genetic analysis confirmed six out of eight patients as X-linked CGD cases with mutations in CYBB gene. A novel splice site mutation was identified in P-07 at position c.141+6 which resulted in the deletion of entire exon 2. Two siblings (P-05 and P-06) from consanguineous parents, were identified with AR-CGD based on the homozygous GT deletion mutation in NCF1 gene.ConclusionsThe clinical presentation, manifestations and genetic subtypes in the local cohort, appear to be comparable with global trends. Mycobacterial infections should be investigated and treated with more prominence. Effective treatment options are required to control the high mortality rate.
Highlights
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of the phagocytic cells, which results in absent or diminished levels of microbicidal reactive oxygen species
We report on the patients with CGD in Sri Lanka, and evaluate the clinical scenario and evolution of the disease in a developing country
Consanguineous marriages are responsible for this high rates of AR-CGD in Turkey and Iran, consanguinity was not frequent among the Indian patients (2/17), and the higher prevalence of AR-CGD may be due to high incidence of autosomal recessive mutations resulting from marriages being restricted to close-knit communities [2]
Summary
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of the phagocytic cells, which results in absent or diminished levels of microbicidal reactive oxygen species. Chronic granulomatous disease (CGD) is a rare, inherited primary immunodeficiency which affects approximately 1/250,000 worldwide [1]. Chronic granulomatous disease is caused by a defect in phagocytic cells (neutrophils, macrophages, and monocytes) which fail to exhibit the ‘respiratory burst’, the rapid increase in oxidative metabolism following phagocytosis, thereby failing to effectively destroy invading pathogens. This is due to a germ line mutation in one of the five genes which code for the five subunits of the NADPH oxidase enzyme complex [1]
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