X-linked chronic granulomatous disease: first report of mutations in patients of Argentina

BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency due to absent or decreased NADPH oxidase activity in phagocytic cells. The X-linked form of the disease (X-CGD) arises from mutations in the CYBB gene, which encodes the 91-kD glycoprotein gp91(phox), the largest component of the oxidase. METHODS: The authors recently started the molecular characterization of X-CGD in 18 patients reported to the Argentinean Registry of Primary Immunodeficiency Diseases. The authors reviewed data from clinical records to examine the relationship of clinical presentation and the type of mutations responsible for the genotype. RESULTS: The frequency and type of infections present in these patients were similar to prior reports. However, pulmonary tuberculosis was observed in the group as well as unusual complications such as eosinophilic cystitis, hepatic abscess with cholangitis, and chronic orchitis. Eleven different mutations in the CYBB gene were identified, and seven of them were novel. The types of mutations were intronic, single-nucleotide substitution resulting in nonsense or missense codons and one or two nucleotide deletions resulting in frameshifts. Molecular studies of 18 mothers revealed X-CGD carrier status in all but 2. CONCLUSIONS: No correlation existed between the type of mutation and the clinical phenotype of the disease: the molecular defects identified resulted in no expression of the flavocytochrome b558 in patients' neutrophils, leading to the X91(o)-CGD phenotype. The lack of gp91(phox) protein could explain the early onset and the severity of the clinical manifestations of CGD in this group of patients from Argentina.     

Chronic granulomatous disease: Clinical,molecular, and therapeutic aspects

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defects in the genes encoding any of the NADPH oxidase components responsible for the respiratory burst of phagocytic leukocytes. CGD is a genetically heterogeneous disease with an X‐linked recessive (XR‐CGD) form caused by mutations in the CYBB gene encoding the gp91^phox protein, and an autosomal recessive (AR‐CGD) form caused by mutations in the CYBA, NCF1, NCF2, or NCF4 genes encoding p22^phox, p47^phox, p67^phox, and p40^phox, respectively. Patients suffering from this disease are susceptible to severe life‐threatening bacterial and fungal infections and excessive inflammation characterized by granuloma formation in any organ, for instance, the gastrointestinal and genitourinary tract. An early diagnosis of and the prompt treatment for these conditions are crucial for an optimal outcome of affected patients. To prevent infections, CGD patients should receive lifelong antibiotics and antifungal prophylaxis. These two measures, as well as newer more effective antimicrobials, have significantly modified the natural history of CGD, resulting in a remarkable change in overall survival, which is now around 90%, reaching well into adulthood. At present, hematopoietic stem cell transplantation (HSCT) is the only definitive treatment that can cure CGD and reverse organ dysfunction. Timing, donor selection, and conditioning regimens remain the key points of this therapy. In recent years, gene therapy (GT) for XR‐CGD has been proposed as an alternative to HSCT for CGD patients without a matched donor. After the failure of the first trials performed with retroviral vectors, some groups have proposed the use of regulated SIN‐lentiviral vectors targeting gp91^phox expression in myeloid cells to increase the safety and efficacy of the GT protocols.     

Chronic granulomatous disease in Latin American patients: clinical spectrum and molecular genetics

BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by early onset of recurrent and severe infections. The molecular defects causing CGD are heterogeneous and lead to absence, low expression, or malfunctioning of one of the phagocyte NADPH oxidase components. The aim of this study was to analyze the clinical features and to investigate the molecular genetic defects of Latin American patients with CGD. PROCEDURES: The study included 14 patients. The diagnosis was based on a history of recurrent severe infections, impaired respiratory burst, and the demonstration of an underlying mutation by single strand conformation polymorphism (SSCP) or RT-PCR analysis, followed by genomic DNA or cDNA sequencing. RESULTS: Seven unrelated patients were found to have the X-linked form of CGD (X-CGD). Heterogeneous mutations affected the CYBB gene: two insertions, one substitution, and four splice site defects; two of them are novel. Seven patients presented with one of the autosomal recessive forms of CGD (A47-CGD); all had the most common mutation, a DeltaGT deletion in exon 2 of the NCF1 gene. Pneumonia was the most frequent clinical feature, followed by pyoderma, sinusitis, otitis, and liver abscess. Patients with X-CGD were more likely to have initial infections before age 2 years and to have inflammatory obstructive granulomas later. None of the patients had severe adverse reactions to BCG immunization. CONCLUSIONS: X-CGD patients from Latin America showed a high degree of molecular heterogeneity, including two novel mutations. Their clinical characteristics included early onset of infections and eventual obstructive granulomas. A47-CGD represented 50% of the reported cases, a higher prevalence than reported in other series.     

Chronische Granulomatose

Genetics. Chronic granulomatous disease is a genetic defect of the NADPH oxidase and therefore of the generation of oxygen radicals in phagocytes. Mutations in four components of this enzyme (gp91phox, p22phox, p47phox, p67phox) could be associated with this disease. Symptoms. Beside the increased susceptibility against infections with catalase-positive agents, patients fibrosis, gastric with CGD suffers frequently from Crohn-like disease, Lupus-like syndromes, pulmonary outlet syndrome and obstructive granulomas of the urinary tract. Therapy. Conservative treatment comprise prophylactic administration of Cotrimoxazole und Itraconazole and under certain circumstances γ-Interferon. Patients with HLA-identical, healthy siblings may be cured with bone marrow transplantation. At the moment there are gene therapeutic attempts, but this method is not clinically available.     

Chorioretinal lesions in patients and carriers of chronic granulomatous disease.

OBJECTIVE: To investigate the frequency of retinal lesions in patients with chronic granulomatous disease (CGD) and to seek such lesions in carriers. STUDY DESIGN: Seventy-four individuals from 33 families were recruited; 38 had CGD (30 X-linked and 8 autosomal recessive inheritance). All participants (including 33 control subjects) underwent measurement of visual acuity, anterior segment examination by slit lamp, and dilated funduscopy. RESULTS: Nine of 38 (23.7%) of the affected children had chorioretinal lesions compared with 0 of 33 control subjects. All 9 were known to have X-linked CGD and absent gp91(phox). The "typical" retinal abnormality consisted of "punched out" chorioretinal lesions associated with pigment clumping lying along major retinal vessels. Unexpectedly, 3 XL-CGD asymptomatic carriers also had typical chorioretinal lesions. CONCLUSION: Retinal lesions are relatively common in patients with XL-CGD and may interfere with vision and thus should be sought in such patients.     

Autosomal recessive chronic granulomatous disease associated with 18q- syndrome and end-stage renal failure due to Henoch-Schönlein nephritis

Chronic granulomatous disease (CGD) is an inherited disorder in which phagocytes, including polymorphonuclear neutrophils, are unable to generate oxygen-derived microbicidal compounds, among them superoxide [1]. Two main types of CGD are known, an X-linked form which is normally associated with the absence of cytochromeb ₅₅₈, a component of the membrane-associated reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase which generates superoxide and an autosomal recessive form, in which cytochromeb ₅₅₈ is present, caused by the deficiency of a cytosolic factor required to activate NADPH oxidase [4]. Patients with the X-linked type are highly susceptible to infections; those with the autosomal recessive form may be less severely affected [10]. We report the unusual association of autosomal CGD with 18q- syndrome in a girl who developed terminal renal insufficiency caused by Henoch-Schönlein nephritis, and speculate on the possibility that the gene defect of autosomal recessive CGD may be located on chromosome 18.     

Severe X-linked chronic granulomatous disease in two unrelated females

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by mutations of one of the subunits of phagocyte reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase leading to decreased or complete absence of neutrophil oxidative burst. We report the clinical and laboratory findings in two young unrelated females 14 and 9 years of age and natives of Tahiti and Reunion Islands, respectively, with severe X-linked granulomatous disease. In both cases, the infectious pattern was unusual, with convergent symptoms suggesting underlying mycobacterial infection. Functional analysis revealed low residual NADPH oxidase activity with about 5–10% of normal neutrophil population. De novo null mutations affecting the CYBB gene that encodes the gp91 protein were found in both cases in the heterozygous state (in patient 1, p.Arg130X in exon 5, and in patient 2, a novel insertion in exon 6, c.632_633insCATC). Methylation analysis confirmed that phenotype expression was linked to skewed X inactivation and showed that the de novo mutation arose on the maternally inherited chromosome in one case and on the paternally inherited chromosome in the other case. In conclusion, X-linked CGD carriers could therefore be at risk for severe infectious diseases depending on the skewed X inactivation pattern and the infectious context.     

Chronic Granulomatous Disease of Childhood: Clinical, Pathological, Biochemical, Molecular, and Genetic Aspects of the Disease

The pathobiology of chronic granulomatous disease (CGD) of childhood, a heterogeneous phenotypic disorder characterized by chronic and recurrent infection, has become more completely understood over the past three decades. Blood neutrophils, monocytes, and eosinophils lack a respiratory burst required for effective killing of catalase positive bacteria by reduced by-products of oxygen. The disease is transmitted in at least two genetic forms: X-linked and autosomal recessive. In the X-linked form, a gene coding for a beta subunit protein required for cytochrome b presence on the plasma membrane of phagocytic cells is not expressed. The protein appears to be a constituent of the cytochrome b complex that requires an additional alpha subunit for complete expression. Cytochrome b is likely a component of leukocyte oxidase, which catalyzes the respiratory burst. The autosomal recessive form of the disorder appears to be controlled by a set of genes coding for soluble cofactors essential for oxidase expression. One or more of these cofactors have recently been shown to be deficient in several patients with autosomal recessive CGD. Optional therapy for CGD patients is presently not available. Long-term use of antibiotics may be helpful. The cloned product interferon gamma has been reported to improve superoxide generation, bactericidal activity, and immunoreactive cytochrome b in some CGD neutrophils and monocytes, both in vitro and in vivo. Currently a prospective clinical evaluation of the efficacy of interferon gamma is in progress. Molecular studies of expression and function of the X-CGD gene in phagocytic cells are in progress as well.     

Chronic granulomatous disease of childhood: clinical, pathological, biochemical, molecular, and genetic aspects of the disease

The pathobiology of chronic granulomatous disease (CGD) of childhood, a heterogeneous phenotypic disorder characterized by chronic and recurrent infection, has become more completely understood over the past three decades. Blood neutrophils, monocytes, and eosinophils lack a respiratory burst required for effective killing of catalase positive bacteria by reduced by-products of oxygen. The disease is transmitted in at least two genetic forms: X-linked and autosomal recessive. In the X-linked form, a gene coding for a beta subunit protein required for cytochrome b presence on the plasma membrane of phagocytic cells is not expressed. The protein appears to be a constituent of the cytochrome b complex that requires an additional alpha subunit for complete expression. Cytochrome b is likely a component of leukocyte oxidase, which catalyzes the respiratory burst. The autosomal recessive form of the disorder appears to be controlled by a set of genes coding for soluble cofactors essential for oxidase expression. One or more of these cofactors have recently been shown to be deficient in several patients with autosomal recessive CGD. Optional therapy for CGD patients is presently not available. Long-term use of antibiotics may be helpful. The cloned product interferon gamma has been reported to improve superoxide generation, bactericidal activity, and immunoreactive cytochrome b in some CGD neutrophils and monocytes, both in vitro and in vivo. Currently a prospective clinical evaluation of the efficacy of interferon gamma is in progress. Molecular studies of expression and function of the X-CGD gene in phagocytic cells are in progress as well.     

Impact of N-acetylcysteine on neonatal cardiomyocyte ischemia-reperfusion injury

Reactive oxygen species (ROS) are hypothesized to play a key role in myocardial ischemia-reperfusion (IR) injury after cardiopulmonary bypass in children. Clinical studies in adults and several animal models suggest that myocardial IR injury involves cardiomyocyte apoptosis and necrosis. This study investigated a potential relationship between IR-induced ROS production and neonatal cardiomyocyte apoptosis using both in vitro and ex vivo techniques. For in vitro experiments, embryonic rat cardiomyocytes (H9c2 cells) exposed to hypoxia-reoxygenation (HR) showed a time-dependent increase in gp91 phox (a marker for ROS production by NADPH oxidases), caspase-3 (a key mediator of apoptosis) expression, and a decrease in the glutathione redox ratio. N-acetylcysteine (NAC; 0.25-2 mM), a potent antioxidant, decreased gp91 phox and caspase-3 expression, inhibited apoptosis and restored the glutathione redox ratio. For ex vivo study, IR injury significantly reduced left ventricular (LV) function and increased the expression of gp91 phox and caspase-3 in Langendorff-perfused neonatal (7-14 d) rabbit hearts. NAC (0.4 mM) treatment completely attenuated LV dysfunction after IR. In summary, neonatal myocardial IR injury is associated with an increase in cardiomyocyte oxidative stress and apoptosis. NAC attenuates apoptosis in an in vitro embryonic rat cardiomyocyte model of HR, and myocardial dysfunction in an ex vivo neonatal rabbit model of myocardial IR injury.     

Prenatal diagnosis and novel mutation in X-linked chronic granulomatous disease

BackgroundChronic Granulomatous Disease (CGD) is a rare primary immunodeficiency caused by the alteration of the enzyme complex NADPH oxidase, which affects the phagocytic function. CGD patients are susceptible to recurrent infections mainly caused by bacteria and/or fungi.MethodsWe studied a 6 year-old boy with suspicion of CGD. The diagnosis was confirmed based on the functional study of NADPH oxidase. Simultaneously, the second pregnancy of the mother was reported and genetic counselling was requested.ResultsWe identified a new disease-causing mutation by direct sequencing of the CYBB gene (X-linked CGD). The prenatal study resulted in the identification of the same mutation in the foetus.CommentsMolecular genetics characterisation of CGD is needed to obtain an accurate diagnosis of the disease and to offer prenatal diagnosis and genetic counselling in future pregnancies.     

Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan

In this paper, we examined the details of severe infections, treatment efficacies, and the prognoses of 23 Japanese patients with chronic granulomatous disease (CGD). We described the mean ages at diagnosis and follow-up, which were 2.8 years (range, 0.7–10 years) and 14.9 years (range, 0.2–28.4 years), respectively. There were three deaths, two from Aspergillus pneumonia and one from liver abscess. Eighteen of the 23 patients (78%) had a complete loss of gp91phox, and three had p22-phox and one had p67phox deficiencies. Aspergillus species were found in 45% of 174 severe infections. The mean height and weight of the 20 surviving patients were −0.8 ± 1.3SD and −1.9 ± 1.9SD below the means for age, respectively. Short stature and underweight (below the 10th percentile of the means) for age were seen in 22% and 17% of the patients, respectively. This growth retardation reflects the severity of the disease. At 20 years of age, there was 87% survival. Ongoing prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) or antifungal drugs was given in 16 and 11 patients, respectively. Interferon-gamma (IFN-gamma) was given once a week to 14 patients. Four patients underwent hematopoietic stem cell transplantation (HSCT) and are currently well. There were infections observed in three of 21 identified related carriers of X-linked CGD. A carrier with a liver abscess had 5% normal neutrophils during the acute phase of infection, which returned to 40% normal neutrophils after recovery. The high survival rate in this hospital results from regular follow-up and prophylaxis with TMP-SMX and anti-fungal drugs beginning at the time of diagnosis, along with treatment with weekly IFN-gamma.     

Spectrophotometric determination of neutrophil cytochrome b558 of chronic granulomatous disease

Abstract Background: Chronic granulomatous disease (CGD) is an inherited disease characterized clinically by severe recurrent bacterial infections from infancy. This disease is a disorder of the formation of superoxide (O₂^-) by the neutrophil NADPH oxidase system, mostly due to defects in cytochrome b₅₅₈ (cyt b₅₅₈), which is one ol the oxidase components. Diagnosis of CGD has been performed by the assay of the O₂^- forming activity. immunological determination of defects in the oxidase components, and or spectrophotometry of cyt b₅₅₈. However, spectrophotometric analysis of the b-type heme is difficult with small amounts of blood from infant CGD patients, as the limited amounts of neutrophils are contaminated with a relatively high ratio of hemoglobin (Hb) that interferes with the heme spectrum of cyt b₅₅₈. This report presents an accurate method foi the spectrophotometric analysis of cyt b₅₅₈ in a small amount of CGD neutrophils that were treated with CO gas in a safe procedure instead of the previously reported CO-bubbling method. Methods and Results: The difference of the reduced minus oxidized cyt b₅₅₈ spectrum was measured under no interference from oxy Hb at the α and β bands and differentiated as d[ΔA]/dΛ, (Λ= wavelength) to obtain further evidence for the defects of the cyt b₅₅₈ heme spectrum. The interference from CO-insensitive met Hb was eliminated by subtracting the absorption peak at the Soret (γ) band of the contaminating met Hb, which was estimated from the CO-treated and untreated spectra of the same, hemolyzed sample. Conclusions: This spectrophotometric method is feasible for the determination of abnormality and heme content of cyt b₅₅₈ with a small amount of CGD neutrophils in10–20 mL of blood even in the presence ol contaminating Hb.     

SOS1 mutation: a new cause of Noonan syndrome

Noonan syndrome, characterized by short stature, facial anomalies, heart disease and cryptorchidism in males, is an autosomal dominant, genetically heterogeneous disease. Approximately 50 % of Noonan syndrome cases are caused by gain-of-function mutations in PTPN11, encoding the tyrosine phosphatase (SHP2) and 5 % are caused by KRAS mutations. Recently, a new mutation in SOS1 gene has been identified in approximately 20 % of cases of Noonan syndrome without PTPN11 mutation. That difference in genotype has a relationship with phenotype that we must investigate. We report a case of Noonan syndrome due to an SOS1 mutation; we describe his phenotype and subsequent outcome.     

Long-term follow-up and outcome of 39 patients with chronic granulomatous disease

OBJECTIVES: To evaluate the clinical long-term course in patients with chronic granulomatous disease (CGD) with respect to different CGD subtypes and currently used antimicrobial prophylactic measures. STUDY DESIGN: The records of 39 patients with CGD who were monitored during a period of 22 years were reviewed. All infections, infectious complications, and clinical outcomes were documented for a total observation period of 610 patient-years and were stratified with respect to different CGD subtypes. RESULTS: Lymphadenitis, skin abscesses, and pneumonia occurred in 87%, 72%, and 59% of the patients, respectively. In 151 microbiologic isolates Staphylococcus aureus, Aspergillus species, Candida species, Pseudomonas species, and Salmonella species were the most frequently detected microorganisms. There were 167 severe infections requiring hospitalization and intravenous antimicrobial treatment, resulting in an incidence of 3.7 severe infections per 100 patient months (SI/100 PM). Long-term antibiotic prophylaxis significantly reduced the incidence of severe bacterial infections from 4.8 SI/100 PM to 1. 6 SI/100 PM (P =.0035). In contrast, fungal infections increased under antibiotic prophylaxis from a mean incidence of 0.2 SI/100 PM to 1.9 SI/100 PM (P =.04). We found a 50% survival rate through the fourth decade of life, with a plateau after the third decade of life. Patients with a complete absence of cytochrome b(558) showed an earlier manifestation of their disease and a higher incidence of infections and had significant lower survival than patients with only diminished cytochrome b(558) or autosomal recessive CGD. CONCLUSIONS: Infections with Aspergillus species have become the major cause of infectious complications and death in patients with CGD. Prophylactic and therapeutic measures are needed to further increase life expectancy and quality for patients with CGD.     

Analysis of various types of chronic granulomatous disease with the monoclonal antibody 7D5 directed against the small subunit of surface cytochrome b558

Four different types of chronic granulomatous disease (CGD) were analysed with the monoclonal antibody, 7D5, directed against the small 23 kD subunit of cytochrome b₅₅₈ using a flow cytometric fluorescence analytical method. 7D5 immunofluorescent surface staining of granulocytes was absent in 12 patients with X-linked cytochrome b₅₅₈ deficiency, in 2 patients with variant X-linked CGD with residual (X-forming activity and in 2 patients with autosomal recessive cytochrome b₅₅₈ deficiency. The mothers of the patients with the X-linked form of CGD had 2 cell populations, one 7D5 negative or weakly positive and one 7D5 positive. The granulocytes of both parents of one patient with autosomal recessive cytochrome b₅₅₈ deficiency had slightly reduced fluorescence intensity comparable to their reduced cytochrome b₅₅₈ content. Three CGD patients with normal cytochrome b₅₅₈ and their parents had granulocytes normally stained with antibody 7D5. 7D5 antibody enables rapid detection and classification of CGD patients with cytochrome b₅₅₈ deficiency as well as rapid identification of heterozygous carriers.     

Fatal hemophagocytic lymphohistiocytosis in X‐linked chronic granulomatous disease associated with a perforin gene variant

A patient with previously unrecognized X‐linked chronic granulomatous disease (X‐CGD) died of multi‐organ failure, secondary to ongoing infection and hemophagocytic lymphohistiocytosis (HLH). Post mortem histological investigations were compatible with X‐CGD, and a CYBB gene mutation was confirmed. No homozygous mutations in the genes encoding perforin (PRF1), MUNC 13‐4 or syntaxin‐11 (STX11) were found; however, there was a heterozygous alteration c.1471G>A in the PRF1 gene causing a p.Asp491Asn substitution. Although this substitution has not been reported to cause primary or secondary HLH, we speculate that it may have made the patient more susceptible for HLH under the circumstances of ongoing infection associated with X‐CGD. Pediatr Blood Cancer 2009;52:527–529. © 2008 Wiley‐Liss, Inc.     

Prevalence, genetics and clinical presentation of chronic granulomatous disease in Sweden

To estimate the prevalence of chronic granulomatous disease (CGD) in Sweden, an inquiry asking for known and possible CGD cases was mailed to paediatric, internal medicine and infectious disease departments all over Sweden. The detected patients were characterized as to genetics and the clinical presentation. Twenty–one patients (belonging to 16 different families) were found, corresponding to a prevalence of ∼ 1/450 000 individuals. The patients with X–linked disease, lacking a functional gp91^phox protein ( n = 12), comprised 57% and 43% of the patients had an autosomal recessive (AR) disease lacking p47^phox ( n = 7) or p67^phox ( n =1), respectively. All unrelated patients with X–linked disease displayed different gene abnormalities such as point mutations predicting nonsense ( n = 3), missense ( n = 1) or splice site mutations ( n = 2), but also a total deletion and a unique 40 base pair duplicature insertion. The patients with p47^phox–deficiency showed a GT deletion at a GTGT tandem repeat, and the p67^phox–deficient patient displayed a heterozygous in–frame deletion of AAG combined with a large deletion in the other allele. Three patients died during the study period, two from Pseudomonas cepacia infections. Patients with X–linked disease had more frequent infections (mean of 1.7 per year), than the patients with AR inheritance (0.5 infections per year). The most common infections were dermal abscesses ( n =111), followed by lymphadenitis ( n =82) and pneumonias ( n =73). Inflammatory bowel disease–like symptoms, mimicking Crohn's disease of the colon, was seen in three CGD patients.     

慢性肉芽肿病基因型与感染病原体的相关性

目的探讨19例慢性肉芽肿病(CGD)患儿临床特点,了解其发病特点、影像学改变、常见感染病原体及基因突变类型。方法对2012年12月至2018年12月在香港大学深圳医院诊断的19例CGD患儿临床表现、实验室检查、治疗及预后资料进行总结分析。结果通过呼吸爆发检查及基因分析明确诊断19例CGD,均为男童。发病年龄≤1个月13例,诊断年龄为2个月~10岁,母亲为携带者16例。临床主要表现为肺部真菌感染(19/19例)、卡介苗病(14/19例)、淋巴结炎(14/19例)、肛周脓肿(9/19例)、皮肤脓肿(5/19例)和溃疡性结肠炎(2/19例)。微生物培养阳性共59例次,其中真菌9例次,肺炎克雷伯杆菌8例次,分枝杆菌7例次,草绿色链球菌5例次,大肠埃希菌3例次,革兰阳性细菌3例次,金黄色葡萄球菌3例次,洋葱伯克霍尔德菌2例次。19例明确基因诊断,其中CYBB 17例、CYBA 1例、NCF21例。无义突变6例,缺失突变5例(大片段缺失2例),剪接突变3例,错义突变5例。其中5种突变类型目前未见报道。本研究中3例剪接突变患儿皮肤、肛周脓肿及淋巴结炎常见,2例大片缺失突变患儿感染较其他患儿严重。结论在国内,CGD主要表现为肺部感染与播散性卡介苗病。感染谱中,分枝杆菌感染较常见;真菌感染占主要部分,呼吸道是最常感染部位;肛周脓肿以肺炎克雷伯杆菌及大肠埃希菌为主,基因突变类型与临床表型关系有待大数据进一步验证。