Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease

Gao, Li; Yin, Qin; Tong, Yue‐Juan; Gui, Jingang; Liu, Xiuyun; Feng, Xing; Yin, Ju; Li, Jun; Guo, Yan; Yao, Yao; Xu, Bin; He, Jianxin; Shen, Kunling; Lau, Yu Lung; Zhou, Jiang

doi:10.1111/pai.13033

Cited by 27 publications

(29 citation statements)

References 28 publications

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“…However, many patients had documented breakthrough infections even while being continued on prophylactic medications. Overall mortality in our cohort was 38.5% which is similar to reports from other countries such as Mexico and China ( 41 , 50 , 56 , 57 ). Our mortality rates are, however, much higher than those reported from the USA, Iran, and European countries.…”

Section: Discussionsupporting

confidence: 88%

Clinical, Immunological, and Molecular Profile of Chronic Granulomatous Disease: A Multi-Centric Study of 236 Patients From India

et al. 2021

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BackgroundChronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment. However, there is lack of multicentric collaborative data on CGD from India.ObjectiveTo describe infection patterns, immunological, and molecular features of CGD from multiple centers in India.MethodsA detailed proforma that included clinical and laboratory details was prepared and sent to multiple centers in India that are involved in the care and management of patients with inborn errors of immunity. Twelve centers have provided data which were later pooled together and analyzed.ResultsOf the 236 patients analyzed in our study, X-linked and AR-CGD was seen in 77 and 97, respectively. Male female ratio was 172:64. Median age at onset of symptoms and diagnosis was 8 and 24 months, respectively. Common infections documented include pneumonia (71.6%), lymphadenitis (31.6%), skin and subcutaneous abscess (23.7%), blood-stream infection (13.6%), osteomyelitis (8.6%), liver abscess (7.2%), lung abscess (2.9%), meningoencephalitis (2.5%), splenic abscess (1.7%), and brain abscess (0.9%). Forty-four patients (18.6%) had evidence of mycobacterial infection. Results of molecular assay were available for 141 patients (59.7%)—CYBB (44.7%) gene defect was most common, followed by NCF1 (31.9%), NCF2 (14.9%), and CYBA (8.5%). While CYBA variants were documented only in Southern and Western parts of India, a common dinucleotide deletion in NCF2 (c.835_836delAC) was noted only in North Indian population. Of the 174 patients with available outcome data, 67 (38.5%) had expired. Hematopoietic stem cell transplantation was carried out in 23 patients, and 12 are doing well on follow-up.ConclusionsIn India, proportion of patients with AR-CGD is higher as compared to Western cohorts, though regional differences in types of AR-CGD exist. Clinical profile and mortality rates are similar in both X-linked and AR-CGD. However, this may be a reflection of the fact that milder forms of AR-CGD are probably being missed.

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Section: Discussionsupporting

confidence: 88%

Clinical, Immunological, and Molecular Profile of Chronic Granulomatous Disease: A Multi-Centric Study of 236 Patients From India

et al. 2021

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“…This report confirms our previous finding that the most common form of CGD in Jordan is the AR type (21). The high frequency of AR-CGD appears also in Tunisia, Egypt, Turkey, Iran, Oman, Saudi Arabia, and Israel because of the high rate of consanguineous marriage in these countries (16,19,23,24,(48)(49)(50)(51) and it is in contrast to the published literature from USA, Europe, South America, China, and Japan, in which X-CGD is the main genetic form (4, 5,17,[25][26][27][52][53][54]. The population in Jordan amounted from 5.3 million in 2004 to 10.2 million in 2020, and is composed of a variety of ethnic groups, the majority being Arabs.…”

Section: Discussionmentioning

confidence: 90%

Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq

et al. 2021

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Chronic granulomatous Disease (CGD) is a rare innate immunodeficiency disorder caused by mutations in one of the six genes (CYBA, CYBB, NCF1, NCF2, NCF4, and CYBC1/EROS) encoding the superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH)—oxidase complex in phagocytes. In the Western population, the most prevalent form of CGD (about two-thirds of all cases) is the X-linked form (X-CGD) caused by mutations in CYBB. The autosomal recessive forms (AR-CGD), due to mutations in the other genes, collectively account for the remaining one-third of CGD cases. We investigated the clinical and molecular features of 22 Jordanian, 7 Libyan, and 2 Iraqi CGD patients from 21 different families. In addition, 11 sibling patients from these families were suspected to have been died from CGD as suggested by their familial and clinical history. All patients except 9 were children of consanguineous parents. Most of the patients suffered from AR-CGD, with mutations in CYBA, NCF1, and NCF2, encoding p22phox, p47phox, and p67phox proteins, respectively. AR-CGD was the most frequent form, in Jordan probably because consanguineous marriages are common in this country. Only one patient from non-consanguineous parents suffered from an X910 CGD subtype (0 indicates no protein expression). AR670 CGD and AR220 CGD appeared to be the most frequently found sub-types but also the most severe clinical forms compared to AR470 CGD. As a geographical clustering of 11 patients from eight Jordanian families exhibited the c.1171_1175delAAGCT mutation in NCF2, segregation analysis with nine polymorphic markers overlapping NCF2 indicates that a common ancestor has arisen ~1,075 years ago.

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“…Our results show the predominance of AR-CGD in the Turkish families investigated. In European series and in China, 68-89% of CGD cases have been reported to be X-linked [8,17]. However, AR-CGD is the predominant form in Turkey and other Mediterranean regions because of the high rate of consanguineous marriages [7][8][9][10].…”

Section: Discussionmentioning

confidence: 99%

Genetic Characteristics, Infectious, and Noninfectious Manifestations of 32 Patients with Chronic Granulomatous Disease

Aygün

Köker

Nepesov

et al. 2020

Int Arch Allergy Immunol

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Background: Chronic granulomatous disease (CGD) is a rare genetic disorder characterized by failure of phagocytic leukocytes to destroy certain microbes. We present a study on CGD patients enrolled at a single medical center concerning the infectious and noninfectious complications and genetic properties of the disease. Methods: Icotinamide adenine dinucleotide phosphate oxidase activity and the expression of flavocytochrome b₅₅₈ were measured by flow cytometry, and clinical outcomes of the patients were listed in relation to the genetic results. Results: The clinical and genetic findings of 32 pediatric cases with CGD from 23 families were enrolled. Pneumonia and anemia were the most common infectious and noninfectious symptoms. Genetic analysis showed that 10 families (43.5%) carried CYBB variants and 13 families (56.5%) have autosomal recessive (AR) CGD, in which 6 families (26%) carried NCF1 variants, 4 (17.4%) carried CYBA variants, and 3 (13%) carried NCF2 variants. The median age of clinical onset was 3.3 and 48 months for patients with X-linked CGD (X-CGD) and AR-CGD, respectively. The onset of symptoms before age 1 year was 94% in X-CGD, 28.5% in AR-CGD, and 12.5% in patients with oxidase residual activity. Moreover, a de novo germline mutation at c.1415delG in CYBB (OMIM#300481) and a novel c.251_263del13bp in CYBA (OMIM#608508) were also investigated. Conclusions: Ihydrorhodamine-1,2,3 assay could not detect carrier mother in de novo case with CYBB variant. Most X-CGD patients have the onset of symptoms before age 1 year. Additionally, residual oxidase activity in AR-CGD causes a delay in onset, diagnosis, and prophylaxis. The protective role of residual activity is limited while the infection is ongoing and becoming serious.

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Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease

Cited by 27 publications

References 28 publications

Clinical, Immunological, and Molecular Profile of Chronic Granulomatous Disease: A Multi-Centric Study of 236 Patients From India

Clinical, Immunological, and Molecular Profile of Chronic Granulomatous Disease: A Multi-Centric Study of 236 Patients From India

Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq

Genetic Characteristics, Infectious, and Noninfectious Manifestations of 32 Patients with Chronic Granulomatous Disease

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