Preliminary study on chronic granulomatous disease in Sri Lanka

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.

Clinical and demographic pattern of chronic granulomatous disease (CGD) from a multicenter perspective: Malaysia’s experience over 26 years

“…7 Primary Immunodeficiency Group, Cluster of Regenerative Medicine, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia. 8 Primary Immunodeficiency Unit, Institute for Medical Research, Kuala Lumpur, Malaysia. 9 Formerly At International Islamic University, Kuantan, Malaysia.…”

<p>Geographic Variability and Pathogen-Specific Considerations in the Diagnosis and Management of Chronic Granulomatous Disease</p>

“…51 , 61 In some of these endemic areas that are resource poor, the inability to distinguish BCG from tuberculosis has led to a possibly higher rate of mortality in CGD patients compared to what is seen in other countries. 62 …”

Clinical and Demographic Pattern of Chronic Granulomatous Disease (CGD) from a Multicenter Perspective: Malaysia’s Experience Over 26 Years

“…Lymphadenitis was the most common clinical presentations in some CGD series. However, in the Malaysian cohort it is the third common presentation [8,19,21,24]. Hepatosplenomegaly is also one of the common physical ndings (30%).…”

“…Mycobacterium tuberculosis infection a icted signi cant proportion of CGD in Sri Lanka, China and South East Asia [8,17,23]. Pulmonary tuberculosis is seen in 77% of CGD in Sri Lanka and 31.7% of CGD in Iran [8,21].…”

“…The mortality of the patients that we could follow up was 25% which was lower than India (35%) [7], Sri Lanka 38% [6], but higher than the European cohort 20% [14]. [8,9,18]. Previous study demonstrated strong association between residual related reactive oxygen intermediates (ROIs) and survival of patients with CGD; where those with little residual production of ROI may fare worse in the severity of illness and survival outcome [39]…”