Clinical and demographic pattern of chronic granulomatous disease (CGD) from a multicenter perspective: Malaysia\u2019s experience over 26 years

Florence Bakon,Asrul Abdul Wahab,Nasuruddin Abdullah ,Suriani Mohamad ,Zarina Thasneem Zainudeen,Norzila Mohamed Zainudin ,Intan Juliana Abd Hamid ,Thiyagar Nadarajaw,Intan Hakimah Ismail ,Lokman Mohd Noh ,Iean Hamzah Sendut,Kamarul Azhar Mohd Razali ,Adiratna Mat Ripen,Faizah Mohamed Jamil,Adli Ali,Rahim Md Noah ,Bilkis Banu Sabd Aziz ,Hasniah Abdul Latif,Amir Hamzah Abdul Latiff,David Chun Ern Ng ,Long Juan Kok,Ilie Fadzilah Hashim,Mohd Azri Zainal Abidin

doi:10.1186/s13223-021-00551-4

Abstract

BackgroundA retrospective review of clinical manifestations and demographic pattern of patients diagnosed as chronic granulomatous disease (CGD) from 7 hospitals in Malaysia. An analysis of the available database would establish clinical characteristics, diagnoses and outcome including microbiologic pattern. Studying the demography allows us to document the occurrence of CGD amongst multiethnic groups and its geographical distribution for Malaysia.MethodsData from the Malaysia Primary Immunodeficiency Network (MyPIN) with cases of CGD diagnosed from 1991 until 2016 were collated and analysed.ResultsTwenty patients were diagnosed as CGD. Males (N = 13, 65%) outnumber females (N = 7, 35%). CGD is commonest amongst the Malays (65%) followed by the Chinese (15.0%), Indians (10.0%) and natives of Borneo (10.0%), reflecting the ethnic composition of the country. The mean age of diagnosis was 3.7 years. There was a positive family history in 40% of the cases. Abscess was the main presenting feature in 16 patients (80%) with one involving the brain. Pneumonia occurred in 10 (50%) and one with complicated bronchiectasis. Catalase-positive bacteria were the most commonly isolated pathogen with Chromobacterium violaceum predominating (N = 5, 25%) with consequent high mortality (N = 4, 80%). All CGD patients with C. violaceum infection displayed CD4 + (T helper cells) lymphopenia.ConclusionThis study has shown CGD occurs in the major ethnic groups of Malaysia. To the best of our knowledge, this is the first and the largest series of chronic granulomatous disease in South East Asia which may be reflective of similar clinical pattern in the region. C. violaceum infection is associated with a higher mortality in CGD patients in Malaysia. All the CGD patients with C. violaceum infection in this patient series displayed CD4 + (T helper) lymphopenia. We recorded rare clinical manifestation of CGD viz. brain abscess and bronchiectasis.

Highlights

A retrospective review of clinical manifestations and demographic pattern of patients diagnosed as chronic granulomatous disease (CGD) from 7 hospitals in Malaysia
Chronic granulomatous disease cases in Malaysia were first reported in 1994 diagnosed in two unrelated boys [4] based on nitroblue tetrazolium dye test (NBT) and chemiluminescence assay (CA); and this would have been the first report from South East Asia (SE Asia)
Defect in p47phox protein expression was documented in 6 patients, which were suggestive of autosomal recessive CGD (NCF1 gene mutation)

Summary

Introduction

A retrospective review of clinical manifestations and demographic pattern of patients diagnosed as chronic granulomatous disease (CGD) from 7 hospitals in Malaysia. Chronic granulomatous disease (CGD) is a genetic disorder resulting from the defect of one of the subunits of enzyme NADPH oxidase. It is responsible for the production of the reactive oxygen species (ROS) by the phagocytes to kill the engulfed pathogen. Few countries in SE Asia (Malaysia, Singapore and Thailand) have published reports of case series of PID which included CGD [3,4,5,6,7]. This report would be the first patient series in SE Asia, revealing some inherent differences in the clinical and demographic patterns from the Europe, America and Asia [2, 8,9,10, 18]

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Discussion

Conclusion