Background
Chronic granulomatous disease (CGD) is a primary immunodeficiency with defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, resulting in compromised respiratory burst necessary for normal killing of microorganisms by phagocytes ( 1 ). This defect is caused by mutations in the genes encoding the NADPH oxidase subunits, including CYBB (gp91 phox ), CYBA (p22 phox ), NCF1 (p47 phox ), NCF2 (p67 phox ), and NCF4 (p40 phox ) ( 1 ). Pathogenic variants in the CYBB gene are inherited in an autosomal recessive manner, while other genes manifest as an autosomal recessive trait ( 2 ).
While autoinflammatory manifestations and peripheral infections are hallmarks of this condition, recent reports confirm that severe invasive infections, such as hepatosplenic abscesses, can also occur, underscoring its phenotypic spectrum ( 3 ). Furthermore, the genetic landscape of CGD has expanded to include defects beyond the core NADPH oxidase complex. For instance, homozygous loss-of-function mutations in CYBC1 (also known as EROS ), a chaperone critical for the stability of gp91phox, result in an autosomal recessive form of CGD with a clinical phenotype akin to classic CYBB -deficiency ( 4 ).
CGD is often accompanied by recurrent, even life-threatening bacterial and fungal infections, with the most common pathogens including Staphylococcus aureus , Serratia marcescens , Burkholderia cepacia complex, Nocardia spp., and Aspergillus species ( 5 ). In patients with CGD, infections trigger exaggerated or dysregulated inflammatory cascades, which can be associated with immune abnormalities such as hypergammaglobulinemia ( 6 ) or less commonly, hypogammaglobulinemia ( 7 ).
Although infections with B. cepacia complex have been commonly reported in patients with CGD, infections due to B. multivorans have rarely been reported, even in immunocompetent patients ( 8 , 9 ). Herein, we report an adolescent with CGD who developed a B. multivorans infection along with significantly elevated immunoglobulin E (IgE) levels.
Case presentation
A 16-year-old boy was referred to this hospital with a two-week history of persistent fever, chills, cough and scant sticky phlegm despite intravenous azithromycin and cefuroxime. Fever (T max 39.5 °C) persisted after escalation of antibiotics to ertapenem and linezolid for six days. Physical examination revealed a normal body mass index (20 kg/m 2 , z-score of −0.18) and distinctive facial features characterized by a wide and thick nose and a full lower lip ( Figure 1a ). The patient's height (173 cm) and weight (60 kg) were both around the 50th percentile, and pubertal development was appropriate for age (Tanner stage IV).
On admission, leukocytosis, elevated C-reactive protein, erythrocyte sedimentation rate, IgA and IgE were noted. Specific IgE showed moderate allergy to Aspergillus fumigatus and mold mix. Galactomannan test, cryptococcus antigen test, Widal test, Chlamydia antibody, Mycoplasma antibody, Legionella antibody, hepatitis panel (HBsAg, HBeAg, anti-HBs, Anti-HBe, Anti-HBc and HCV), parvovirus B19 antibody, cytomegalovirus DNA, Epstein–Barr virus DNA, sputum culture and a total of three sets of peripheral blood culture were all negative ( Table 1 ). Chest CT revealed left lower lobe consolidation suggestive of pneumonia ( Figure 1b ).
Table 1
Laboratory findings of the patient with a rare compound heterozygote mutation in the CYBA gene on admission.
| Variable | Detection value | Reference range |
| White blood cell count (× 10 9 /L) | 11.8 | 3.5–9.5 |
| Platelet count (× 10 9 /L) | 229 | 100–350 |
| Neutrophils (%) | 80 | 50–75 |
| Eosinophils (%) | 0.5 | 0.5–5 |
| C-reactive protein (mg/L) | 77.1 | ≤ 8 |
| Procalcitonin (ng/mL) | < 0.072 | - |
| Erythrocyte sedimentation rate (mm/hour) | 32 | 0–15 |
| Immunoglobulin G | 15.95 | 7–17 |
| Immunoglobulin A | 8.17 | 0.7–4 |
| Immunoglobulin M | 1.02 | 0.4–2.3 |
| Immunoglobulin E | > 5,000 | 0–60 |
He had two prior admissions for pneumonia in the preceding six months, which responded to antibiotics including azithromycin, cephalosporin, piperacillin-tazobactam and meropenem. His past medical history included two acute flares of eczema per year between 3 and 10 years of age. Oral ulcers occurred frequently ages 8–14 years without genital involvement. He also developed seasonal rhinitis. No specific family history was reported.
After admission, he received intravenous ceftazidime 1 g every 8 h, azithromycin 250 mg once daily and vancomycin 1 g every 12 h but the fever persisted ( Figure 2 ). Bronchoscopy showed no abnormality, and bronchoalveolar lavage fluid (BALF) cultures were negative. DNA extracted from BALF (QIAamp DNA Microbiome Kit, QIAGEN, Germany) underwent mNGS on an Illumina NovaSeq 6000 (Illumina, San Diego, USA). After filtering low-quality reads and human DNA, B. multivorans was identified (34 reads, 35.2% relative abundance, 72.5% genome coverage, and 2.3 × depth). This organism was not a background contaminant and was unique to this sample, supporting result reliability. Transbronchial lung biopsy of the left lower lobe showed inflammation accompanied by focal neutrophil infiltration ( Figure 1c ). Based on these results, antibiotics were switched to oral trimethoprim/sulfamethoxazole (SXT) 800 mg/160 mg four times daily and ceftazidime 2 g every 8 h based on the identified pathogen. His temperature normalized within two days ( Figure 2 ). Repeat thorax CT showed marked resolution of consolidation in the left lower lobe ( Figure 1b ).
Considering a young age and recurrent episodes of pneumonia, we suspected an inborn error of immunity. Whole exome sequencing (WES) was performed on the patient and his parents. The patient was found to be a compound heterozygote for two mutations in the CYBA gene (chromosome 16, exon 1 and 6), which encodes the protein p22 phox ( Figure 1d ). The mutations were: c.7C > T in exon 1 [Gln3 > Ter], and c.371 C > T in exon 6 [Ala124 > Val] ( 10 , 11 ). His mother carried the first mutation, and his father the second ( Figure 1e ). Flow cytometric dihydrorhodamine neutrophil respiratory burst assay, performed according to the published protocol ( 12 ), showed severely impaired neutrophil hydrogen peroxide production. To quantify the magnitude of the defect, we calculated the stimulation index (SI) by dividing the mean fluorescence intensity (MFI) of PMA-stimulated neutrophils by that of unstimulated cells. Prior to HSCT, the patient's neutrophil respiratory burst index was 8.17, which is only approximately 2.7% of the normal control value (300.89), indicating a profound defect in NADPH oxidase activity ( Figure 1f ). No pathogenic or likely pathogenic variants in STAT3 were identified after careful review. Given the diagnosis of CGD and his high risk of recurrent infections, prophylactic oral antibiotics and itraconazole were prescribed at discharge.
Despite good adherence to the prophylactic regimen, the patient experienced recurrent fevers upon discontinuation of the medications. Eight months after discharge, the patient underwent allogeneic HSCT from his father, who was a 5/10 HLA-matched donor and ABO incompatible (donor: B positive; recipient: O positive). The transplantation was performed at a specialized center following multidisciplinary discussion and informed consent. Serial assessments of neutrophil function using the dihydrorhodamine respiratory burst assay showed restoration of NADPH oxidase activity to 97.3% at a month post-HSCT and 93.2% at six months. Immunoglobulin (IgG, IgA, IgM and IgE) monitoring, hematopoietic and immunological reconstitution post-HSCT demonstrated expected recovery ( Figures 3 , 4 ). Long-term prophylactic medications with antimicrobials and immunosuppressants was carefully tapered based on immune reconstitution: antibacterial prophylactic medications (levofloxacin, isoniazid, SXT) was discontinued 4–16 months post-HSCT, antiviral (acyclovir) and antifungal (itraconazole) prophylactic medications at one year, and ciclosporin at 22 months. Complete withdrawal of prophylactic medications represents a major milestone and a key benefit of curative HSCT, eliminating the lifelong toxicities, costs, and burdens of sequelae. This immune restoration translated into a profound improvement in his quality of life. The patient remained free of CGD-related infections, returned to school and sports, and continued regular clinical and laboratory surveillance. At his most recent evaluation, 25 months post-HSCT and 4 months after stopping all prophylaxis, he remained clinically well, with no relapse or opportunistic infections.
Discussion and conclusions
CGD is a rare but potentially fatal primary immunodeficiency. The estimated incidence in the USA and Europe is around 1 in 200,000 births, whereas no incidence data are available for China ( 13 ). The respiratory burst assay is a key screening tool ( 14 ), and abnormal results should be confirmed by genetic analysis. However, in adult-focused hospital settings where the assay is often unavailable, genetic sequencing may be a more practical diagnostic approach, as illustrated by our patient.
Heterozygous and homozygous c.7C > T in exon 1 [Gln3 > Ter] have been reported in patients with CGD in China ( 10 ) and Japan ( 11 ); homozygous c.371 C > T in exon 6 [Ala124 > Val] has also been reported in Asian and African CGD cohorts ( 15 – 17 ). However, the combination of heterozygous c.7C > T (Gln3 > Ter) and c.371 C > T (Ala124 > Val) in the CYBA gene is reported here for the first time. According to the American College of Medical Genetics guidelines, the nonsense mutation CYBA : c.7C > T (Gln3 > Ter) can be classified as pathogenic (PVS1 + PM2 + PM3) ( 11 , 18 ). The variant c.371 C > T (Ala124 > Val) was further analyzed using multiple bioinformatic tools. Conservation analysis shows the alanine at position 124 is highly conserved across mammals. PolyPhen-2 and SIFT predicted the variant c.371 C > T (Ala124 > Val) as “uncertain”, with scores of 0.38 and 0.011, respectively. REVEL and AlphaMissense predicted the variant c.371 C > T (Ala124 > Val) as “deleterious (moderate)”, with scores of 0.83 and 0.97. According to the previous studies ( 19 ), REVEL scores can provide PP3 evidence if they meet calibrated thresholds: 0.644–0.772 suggests “supporting pathogenic evidence”; 0.773–0.931 suggests “moderate pathogenic evidence”; and > 0.932 suggests “strong pathogenic evidence”. Thus c.371C > T with a REVEL score of 0.83 qualifies as PP3 Moderate. Taken together, for CYBA :c.371C > T, its trans configuration with CYBA :c.7C > T supports PM3 evidence, allowing it to be classified as likely pathogenic (PM2 + PP3_Moderate + PM3).
Hyper IgE syndrome (HIES) typically presents with elevated serum IgE, eczematous rash, recurrent pneumonia, and characteristic dysmorphic features such as red-hair, retained primary dentition, a high-arched palate, and recurrent oral candidiasis ( 20 ). CGD is characterized by impaired or absent reactive oxygen species production in all phagocytes, predisposing patients to recurrent bacterial and fungal infections ( 21 ). Both HIES and CGD can present with recurrent infection. The NIH HIES scoring system, proposed by Grimbacher et al. ( 22 ) aids in screening. Scores ≥ 40 points strongly suggest HIES, scores < 20 make HIES diagnosis unlikely, and scores 20–40 are inconclusive. This patient exhibited some HIES-like features, including facial appearance, significantly elevated IgE, and positive Aspergillus precipitating IgG, which could be misleading. But he did not exhibit characteristic HIES features such as retained primary teeth, recurrent candidiasis, or skeletal abnormalities. His HIES-NIH score was 29, placing him in the grey zone. The final diagnosis of CGD was confirmed via CYBA gene mutations and deficient neutrophil function testing. Similarly, Patiroglu T et al. ( 23 ) reported a case of a 9-year-old boy who presented with a characteristic facial appearance, recurrent pneumonia, and elevated IgE levels (HIES-NIH score of 30). Neutrophil function test and molecular analysis revealing a CYBB splice site mutation (c.338-1G > A) confirmed X-linked CGD ( 23 ). Unlike our patient, that boy was born to consanguineous parents, became symptomatic in the second month of life, and experienced severe infections requiring intensive care, highlighting that patients with autosomal recessive CGD generally have a milder phenotype than X-linked CGD ( 21 ).
In this case, mNGS detected B. multivorans in BALF, guiding management of his non-resolving pneumonia. B. multivorans is rarely isolated in humans compared to other species like B. cepacia . A literature review of B. multivorans infections was conducted through the Medline/PubMed database. Fourteen studies met the criteria, comprising 12 sporadic cases and 2 outbreaks ( Table 2 ). The age of patients ranged from 1 to 61 years, with no clear sex predominance. B. multivorans was most frequently isolated from sputum (7/12, 58.3%), followed by blood (2/12, 16.7%), urine, ascitic fluid, tissue and cerebrospinal fluid, no cases were diagnosed by molecular methods. All but one patient had underlying conditions, most commonly cystic fibrosis. Five patients were immunocompromised, including four post-transplant patients and one hematologic malignancy. Treatment regimens varied (cephalosporins, sulfonamides, carbapenems, and others). Most patients responded well to the treatment though two patients died. Regarding outbreaks, one study reported B. multivorans ST1071 contamination of ultrasound gel, leading to bloodstream infections in four pediatric patients in India ( 24 ). Another described clonal spread of B. multivorans ST439 with poor outcomes — 11 of 46 (24%) infected patients died ( 25 ). Literature indicates that B. cepacia complex exhibits intrinsic resistance to many antimicrobials, including penicillins, polymyxins, and aminoglycosides, due to efflux pumps ( 26 ). SXT, meropenem, doripenem, doxycycline, minocycline, and ceftazidime are among the most active agents ( 26 ). SXT combined with an increased dose of ceftazidime successfully controlled his fever and resolved the pneumonia, and he was maintained on long-term SXT and itraconazole to prevent further bacterial and fungal infections ( 1 ).
Table 2
Review of the literature of Burkholderia multivorans infections.
CSF, cerebrospinal fluid; M, male; F, female.
| No. | Year | Location | Age (years)/Sex | Specimen | Co-infection | Clinical manifestaion | Underlying disease | Treatment | Outcome |
| 1 | 2004 | India | 53/M | Ascitic fluid | None | Fever, abdominal pain | Hepatitis C, cirrhosis with portal hypertension | Meropenem | Recovered |
| 2 | 2005 | UK | 40/F | Sputum | Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis | Chronic cough | Acute bronchitis, mild asthma, mannose binding lectin deficiency | Tobramycin and ceftazidime | Recovered |
| 3 | 2018 | USA | 55/M | CSF | None | Fever, chills, nausea, vomiting and abdominal pain | Multiple myeloma | Trimethoprim/sulfamethoxazole | Recovered |
| 4 | 2018 | Sweden | 57/M | Urine | None | Dysuria and fever | None | Trimethoprim-sulfamethoxazole | Recovered |
| 5 | 2019 | Canada | 23 month/M | Blood, lung tissue | None | Fever | Liver transplant, biliary atresia and Kasai surgery | Cefotaxime, piperacillin/tazobactam, tobramycin, ceftazidime, ciprofloxacin, meropenem, vancomycin and sulfamethoxazole/trimethoprim | Died |
| 6 | 2022 | Spain | 61/M | Sputum, bronchoscopic aspirates | None | Not mentioned | Bronchiectasis, lung transplant | Nebulized ceftazidime and inhaled tobramycin | Recovered |
| 7 | 2006 | Germany | 30/M | Sputum | None | Not mentioned | Cystic fibrosis | Not mentioned | Not mentioned |
| 8 | 2011 | UK | 18/F | Sputum | Pseudomonas aeruginosa and Staphylococcus aureus | Fever | Cystic fibrosis | Not mentioned | died |
| 9 | 2013 | USA | 30/M | Sputum | None | Not mentioned | Cystic fibrosis | Not mentioned | Not mentioned |
| 10 | 2018 | UK | not mentioned | Sputum | Pseudomonas aeruginosa and Candida albicans | Shortness of breath and cough | Cystic fibrosis | Ceftazidime/avibactam combined with aztreonam | Recovered |
| 11 | 2019 | Italy | 32/F | Blood | None | Headache | Cystic fibrosis, lung transplant | Meropenem, trimethoprim-sulfamethoxazole, levofloxacin, ceftazidime/avibactam | Recovered |
| 12 | 2020 | USA | 16/F | Sputum | None | Not mentioned | Cystic fibrosis, liver transplant | Meropenem-vaborbactam, nitric oxide | Recovered |
HSCT still remains the curative treatment for patients with CGD ( 27 ), and risks and benefits must be carefully weighed. Gene therapy for hematopoietic cells (GT-HSC) offers a potential alternative, though it is not yet widely available for routine clinical use ( 1 ). Our patient's successful outcome aligns with and extends recent evidence on HSCT for CGD. Chiesa et al. ( 28 ) demonstrated that HLA-matched HSCT yields excellent survival, especially in younger patients, while highlighting increased risks with HLA-mismatched donors. In the absence of a fully matched donor, our case reflects the growing role of haploidentical HSCT, as investigated by Riller et al. ( 29 ). Their study showed that HLA-haploidentical transplantation is a feasible curative option, with 3-year over survival of 75.9%, despite a notable incidence of graft failure and acute graft-versus-host disease (GVHD) ( 29 ). Importantly, our patient did not develop acute or chronic GVHD, underscoring that with careful donor selection, conditioning, and post-transplant management, haploidentical HSCT can yield outcomes approaching those of matched transplants. These findings reinforce that haploidentical HSCT should be considered a viable and potentially curative strategy for patients with CGD lacking HLA-identical donors, particularly when performed early in the disease course.
In conclusion, we present a case of adolescent CGD with a rare compound heterozygous CYBA mutation mimicking HIES, successfully cured by HSCT. The application of mNGS facilitated early identification of B. multivorans and timely initiation of appropriate therapy. Because CGD and HIES can share overlapping clinical and laboratory features, early whole-exome sequencing (WES) is crucial for accurate diagnosis.
Funding Statement
The author(s) declared that financial support was received for this work and/or its publication. This study was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0532800), Peking Union Medical College Hospital Talent Cultivation Program Category D (UHB12396), National Science Foundation for Young Scientists of China (82202541) and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-048). This funding source had no role in the study design or execution, analyses, interpretation of the data, or decision to submit results.
Footnotes
Edited by: Reem Elfeky , Royal Free Hospital, United Kingdom
Reviewed by: Horst von Bernuth , Charité University Medicine Berlin, Germany
Omar Josué Saucedo Ramírez , Hospital Español, Mexico
Data availability statement
The data presented in the study are deposited in the NCBI ClinVa repository, accession number VCV000068212.10 ( https://www.ncbi.nlm.nih.gov/clinvar/variation/68212/?term=SCV007595871 ) and VCV000002264.14 ( https://www.ncbi.nlm.nih.gov/clinvar/variation/2264/?term=SCV007596017 ).
Ethics statement
The studies involving humans were approved by Peking Union Medical College Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants' legal guardians/next of kin. Written informed consent was obtained from the minor(s)' legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.
Author contributions
MZ: Conceptualization, Funding acquisition, Writing – original draft. YZ: Writing – review & editing. XS: Writing – review & editing. WM: Methodology, Writing – review & editing. YL: Formal analysis, Methodology, Software, Writing – review & editing. CS: Writing – review & editing. ZL: Resources, Writing – review & editing. YC: Funding acquisition, Writing – review & editing. XT: Writing – review & editing. JF: Conceptualization, Writing – review & editing. JW: Writing – review & editing.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Yu HH, Yang YH, Chiang BL. Chronic granulomatous disease: a comprehensive review. Clin Rev Allergy Immunol. (2021) 61(2):101–13. 10.1007/s12016-020-08800-x
2. van de Geer A, Nieto-Patlan A, Kuhns DB, Tool AT, Arias AA, Bouaziz M, et al. Inherited p40phox deficiency differs from classic chronic granulomatous disease. J Clin Invest. (2018) 128(9):3957–75. 10.1172/JCI97116
3. Chakkyar K, Saravanan P, Habeeb AM, Manakkad SP, Edavazhippurath A, Pradhan RK, et al. Hepatosplenic abscesses in a child with p40(phox) deficiency due to a homozygous NCF4 variant. Pediatr Allergy Immunol. (2025) 36(10):e70226. 10.1111/pai.70226
4. Arnadottir GA, Norddahl GL, Gudmundsdottir S, Agustsdottir AB, Sigurdsson S, Jensson BO, et al. A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease. Nat Commun. (2018) 9(1):4447. 10.1038/s41467-018-06964-x
5. Roos D. Chronic granulomatous disease. Methods Mol Biol. (2019) 1982:531–42. 10.1007/978-1-4939-9424-3_32
6. Seger RA. Modern management of chronic granulomatous disease. Br J Haematol. (2008) 140(3):255–66. 10.1111/j.1365-2141.2007.06880.x
7. Hanoglu D, Ozgur TT, Ayvaz D, Koker MY, Sanal O. Chronic granulomatous disease presenting with hypogammaglobulinemia. J Investig Allergol Clin Immunol. (2011) 21(4):310–2.
8. Xu X, Lu B, Xie Y, Yang D, Lu G, Fan H. A novel mutation in CYBB induced X-linked chronic granulomatous disease: a case report. Respir Med Case Rep. (2020) 31:101213. 10.1016/j.rmcr.2020.101213
9. Urriola N, Williams A, Keat K. Macrophage activation syndrome/haemophagocytic lymphohistiocytosis secondary to Burkholderia cepacia complex septicaemia in an elderly female carrier of X-linked chronic granulomatous disease with extreme lyonisation: ‘cepacia syndrome’ revisited. BMJ Case Rep. (2019) 12(8):e230434. 10.1136/bcr-2019-230434
10. Gao LW, Yin QQ, Tong YJ, Gui JG, Liu XY, Feng XL, et al. Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease. Pediatr Allergy Immunol. (2019) 30(3):378–86. 10.1111/pai.13033
11. Yamada M, Ariga T, Kawamura N, Ohtsu M, Imajoh-Ohmi S, Ohshika E, et al. Genetic studies of three Japanese patients with p22-phox-deficient chronic granulomatous disease: detection of a possible common mutant CYBA allele in Japan and a genotype-phenotype correlation in these patients. Br J Haematol. (2000) 108(3):511–7. 10.1046/j.1365-2141.2000.01857.x
12. Xiaohui W, Shunying Z, Xiaoyan Z, Xiaolei T, Yuelin S, Jinrong L, et al. The value of DHR-enzyme-linked immunosorbent assay in the diagnosis of chronic granulomatous disease by detecting NADPH oxidase complex activity. Front Pediatr. (2025) 13:1483173. 10.3389/fped.2025.1483173
13. Rider NL, Jameson MB, Creech CB. Chronic granulomatous disease: epidemiology, pathophysiology, and genetic basis of disease. J Pediatric Infect Dis Soc. (2018) 7(suppl_1):S2–5. 10.1093/jpids/piy008
14. Yu JE, Azar AE, Chong HJ, Jongco AM, 3rd, BT P. Considerations in the diagnosis of chronic granulomatous disease. J Pediatric Infect Dis Soc. (2018) 7(suppl_1):S6–11. 10.1093/jpids/piy007
15. Chiu TL, Leung D, Chan KW, Yeung HM, Wong CY, Mao H, et al. Phenomic analysis of chronic granulomatous disease reveals more severe integumentary infections in X-linked compared with autosomal recessive chronic granulomatous disease. Front Immunol. (2021) 12:803763. 10.3389/fimmu.2021.803763
16. Roos D, Kuhns DB, Maddalena A, Bustamante J, Kannengiesser C, de Boer M, et al. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (second update). Blood Cells Mol Dis. (2010) 44(4):291–9. 10.1016/j.bcmd.2010.01.009
17. Koker MY, Camcioglu Y, van Leeuwen K, Kilic SS, Barlan I, Yilmaz M, et al. Clinical, functional, and genetic characterization of chronic granulomatous disease in 89 turkish patients. J Allergy Clin Immunol. (2013) 132(5):1156–63 e5. 10.1016/j.jaci.2013.05.039
18. Kim YM, Park JE, Kim JY, Lim HK, Nam JK, Cho M, et al. Genetic analysis of 10 unrelated Korean families with p22-phox-deficient chronic granulomatous disease: an unusually identical mutation of the CYBA gene on Jeju Island, Korea. J Korean Med Sci. (2009) 24(6):1045–50. 10.3346/jkms.2009.24.6.1045
19. Pejaver V, Byrne AB, Feng BJ, Pagel KA, Mooney SD, Karchin R, et al. Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3/BP4 criteria. Am J Hum Genet. (2022) 109(12):2163–77. 10.1016/j.ajhg.2022.10.013
20. Minegishi Y. Hyper-IgE syndrome, 2021 update. Allergol Int. (2021) 70(4):407–14. 10.1016/j.alit.2021.07.007
21. Blancas-Galicia L, Santos-Chavez E, Deswarte C, Mignac Q, Medina-Vera I, Leon-Lara X, et al. Genetic, immunological, and clinical features of the first Mexican cohort of patients with chronic granulomatous disease. J Clin Immunol. (2020) 40(3):475–93. 10.1007/s10875-020-00750-5
22. Grimbacher B, Schaffer AA, Holland SM, Davis J, Gallin JI, Malech HL, et al. Genetic linkage of hyper-IgE syndrome to chromosome 4. Am J Hum Genet. (1999) 65(3):735–44. 10.1086/302547
23. Patiroglu T, Gungor HE, Lazaroski S, Unal E. Chronic granulomatous disease with markedly elevated IgE levels mimicking hyperimmunoglobulin E syndrome. Acta Microbiol Immunol Hung. (2013) 60(2):155–62. 10.1556/AMicr.60.2013.2.6
24. Dogra S, Angrup A, Kanaujia R, Vig S, Kaur R, Paul RA, et al. Burkholderia multivorans sepsis outbreak in a neonatal surgical unit of a tertiary care hospital. Indian J Pediatr. (2021) 88(7):725. 10.1007/s12098-021-03757-x
25. Hanulik V, Webber MA, Chroma M, Uvizl R, Holy O, Whitehead RN, et al. An outbreak of Burkholderia multivorans beyond cystic fibrosis patients. J Hosp Infect. (2013) 84(3):248–51. 10.1016/j.jhin.2013.04.001
26. Sfeir MM. Burkholderia cepacia complex infections: more complex than the bacterium name suggest. J Infect. (2018) 77(3):166–70. 10.1016/j.jinf.2018.07.006
27. Dedieu C, Albert MH, Mahlaoui N, Hauck F, Hedrich C, Baumann U, et al. Outcome of chronic granulomatous disease - conventional treatment vs stem cell transplantation. Pediatr Allergy Immunol. (2021) 32(3):576–85. 10.1111/pai.13402
28. Chiesa R, Wang J, Blok HJ, Hazelaar S, Neven B, Moshous D, et al. Hematopoietic cell transplantation in chronic granulomatous disease: a study of 712 children and adults. Blood. (2020) 136(10):1201–11. 10.1182/blood.2020005590
29. Riller Q, Hauri M, Lum SH, Knippenberg J, Sirait T, Laberko A, et al. HLA-haploidentical stem cell transplantation for chronic granulomatous disease: an EBMT-IEWP retrospective study. Blood. (2025) 145(21):2518–27. 10.1182/blood.2024026915
Associated Data
Data Availability Statement
The data presented in the study are deposited in the NCBI ClinVa repository, accession number VCV000068212.10 ( https://www.ncbi.nlm.nih.gov/clinvar/variation/68212/?term=SCV007595871 ) and VCV000002264.14 ( https://www.ncbi.nlm.nih.gov/clinvar/variation/2264/?term=SCV007596017 ).