Chronic granulamatous disease: Two decades of experience from a paediatric immunology unit in a country with high rate of consangineous marriages

Abstract

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by susceptibility to bacterial and fungal infections resulting from the inadequacy of phagocytic leucocytes to produce reactive oxygen radicals. CGD is a genetically heterogeneous disease with an X‐linked recessive (XR‐CGD) form caused by mutations in the CYBB (OMIM #300481) gene encoding the gp91(phox) protein, and an autosomal recessive (AR‐CGD) form caused by mutations in the CYBA (OMIM #608508), NCF1 (OMIM #608512), NCF2 (OMIM #608515) and NCF4 (OMIM #601488) genes encoding p22(phox), p47(phox), p67(phox) and p40(phox), respectively. The genetic mutation of one of the cytosolic p47phox/p67phox proteins and membrane‐bound gp91phox/p22phox proteins, which constitutes the NADPH oxidase enzyme complex, causes the disease. In this study, we evaluated the clinical, laboratory and genetic findings and the prognostic effects of molecular inheritance of our 24 CGD cases (14 XR, 10 autosomal recessive‐AR). Consanguinity (three XR and all AR cases) showed statistically significant relationship with the type of hereditary inheritance (P < 0.001). 83% patients had an infection since early infancy. The mean age of initiation of symptoms was earlier in XR cases, and 78% patients had respiratory tract infections. Bone marrow transplantation was performed in five XR cases (two ex) and four AR (one ex) cases. Three of nine XR and two of six AR cases deceased on medical follow‐up. In countries especially with high consanguinity rates, the early diagnosis for appropriate prophylactic treatment of CGD is quietly important to avoid from recurrent severe infections, early death and fatal complications of late transplantation.

Hematopoietic Cell Transplantation for Chronic Granulomatous Disease in Japan

“…These severe general conditions before and at the time of HCT might have been an influence contributing to the poor outcome of non-CYBB CGD patients in the present study. There are also possible differences in the outcomes of HCT for CGD with non-CYBB gene mutations between countries; thus, these mutations are associated with lower incidence of GF and death after HCT in other countries [ Table S2; (4,5,15,17,18)]. It is necessary to evaluate the outcomes of HCT for CGD patients with non-CYBB gene mutations in detail internationally, because of rarity of these gene mutation subtypes of CGD.…”

Microbiological profile in chronic granulomatous disease patients in a single Brazilian primary immunodeficiency center

“…2,3 Autosomal recessive inheritance is more common in countries with high frequency of consanguinity. [10][11][12] In a Turkish study, 11 consanguinity was reported by 13 of the 24 patients (54%), and 10 out of 13 patients had an autosomal recessive form of the disease. In this cohort, history of consanguinity in the family was reported by only three patients.…”

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

“…However, in Israel, Saudi Arabia, Libya, Oman, Iran, and India, the AR47 0 CGD form prevails (16,24,48,51,59,64,65). However, in Turkey about 30-40% of the CGD patients have X-CGD, but AR47 0 CGD represents about 30-50% of AR-CGD too (19,75,76). We have no clear explanation yet for this discrepancy apart from the appearance of ancestral mutations such as the c.1171_1175delAAGCT mutation in NCF2 in Jordan and close countries and probably the same is true for the c.295_301 delGTGCCCG mutation in CYBA.…”