Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic granulomatous disease (CGD) is characterized by defects in the superoxide producing enzyme NADPH oxidase causing phagocytes to improperly clear invading pathogens. Here we report findings of a late presenting 16-year-old female with X-linked CGD. The patient presented with community-acquired pneumonia, but symptoms persisted for 2 weeks during triple antimicrobial coverage. Cultures revealed Aspergillus fumigatus which was resolved through aggressive voriconazole treatment. Neutrophil studies revealed NADPH oxidase activity and flavocytochrome b(558) levels that were 4-8% of controls and suggested carrier status of the mother. We found a null mutation in the CYBB gene (c.252insAG) predicting an aberrant gp91(phox) protein (p.Cys85fsX23) in the heterozygous state. Methylation analysis demonstrated extremely skewed X chromosome inactivation favoring the maternally inherited defective gene. In conclusion, a novel mutation in the CYBB gene and an extremely skewed X-inactivation event resulted in the rare expression of the CGD phenotype in a carrier female.
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PMID:X-linked chronic granulomatous disease secondary to skewed X chromosome inactivation in a female with a novel CYBB mutation and late presentation. 1900 69

Patients with hyperimmunoglobulin E syndrome (HIES) and chronic granulomatous disease (CGD) have prominently increased immunoglobulin (Ig) E levels. We present a 9-year-old boy with medical history revealing recurrent pneumonia, suppurative lymphadenitis, diarrhea, and otitis. The patient was hospitalized with severe pneumonia. The examination showed tachypnea, crackles at the right and left base of the lung, freckles on his face, red-hair, gingivitis, a high arched palate, and retained primary dentition. Serum IgE level was markedly increased. Nevertheless, patient did not have STAT3 or DOCK8 mutation, characteristic of HIES. Neutrophil function test with dihydrorhodamine (DHR) showed X linked-CGD pattern and molecular analysis of DNAshowed a splice site mutation (c.338-1G > A) in CYBB gene. Herein, we present a case of CGD with selective IgA deficiency. Laboratory findings and elevated IgE mimic the features seen in HIES. Thus, CGD must be considered as a differential diagnosis in patients with elevated Ig E.
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PMID:Chronic granulomatous disease with markedly elevated IgE levels mimicking hyperimmunoglobulin E syndrome. 2382 47

We present a case of refractory pneumonia in an adult patient with underlying chronic granulomatous disease (CGD). Her lobectomy tissue grew B urkholderia cepacia and histopathology revealed diffuse severe pneumonic consolidation with suppurative/necrotizing granulomata. An initial attempt to find an underlying immune deficiency was unsuccessful. Following recurrent invasive infections, repeat immunological assessment revealed reduced neutrophil function, demonstrating skewed carrier status (lyonization) for X-linked CGD (only 3% normal cells). A pathogenic mutation in the CYBB gene was found on sequencing. CYBB gene encodes the gp91phox, a catalytic subunit of nicotinamide adenine dinucleotide phosphate-oxidase that produces reactive oxygen species in phagocytes. Lyonization increases with age, explaining the delayed clinical CGD. CGD is a rare neutrophil disorder that usually presents in early life with recurrent infections due to bacteria and fungi primarily involving lungs and skin. It is secondary to a defective NADPH oxidase system needed to kill intracellular organisms and activate the formation of neutrophil extracellular traps.
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PMID:Chronic granulomatous disease presenting as refractory pneumonia in late adulthood. 2609 Jan 11

Hypersensitive pneumonitis (HP) is a rare initial presentation of chronic granulomatous disease (CGD), especially in children. CGD presenting as HP may result from exposure to inhaled environmental antigens and be induced by excessive production of inflammatory cytokines due to loss of reactive oxygen species production. We herein describe a 2-year-old boy with CGD caused by a mutation in CYBB gene, who initially presented with HP. The patient developed dry cough, progressive dyspnea, and fever after playing in dusty air in a factory that produced plastic materials containing isocyanates. The patient's symptoms and radiological abnormalities did not improve after antigen avoidance, but disappeared after corticosteroid therapy. Because HP is uncommon in children, we should consider the possibility of CGD in children who present with HP. A prompt diagnosis of CGD is essential to enable initiation of prophylactic antibacterial and antifungal therapies.
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PMID:Hypersensitive Pneumonitis: an Initial Presentation of Chronic Granulomatous Disease in a Child. 2930 45

Recurrent severe bacterial and fungal infections are characteristic features of the rare genetic immunodeficiency disorder chronic granulomatous disease (CGD). The disease usually manifests within the first years of life with an incidence of 1 in approximately 200,000 live births. The incidence is higher in Iran and Morocco where it reaches 1.5 per 100,000 live births. Mutations have been described in the 5 subunits of NADPH oxidase, mostly in gp91phox and p47phox, with fewer mutations reported in p67phox, p22phox, and p40phox. These mutations cause loss of superoxide production in phagocytic cells. CYBB, the gene encoding the large gp91phox subunit of the transmembrane component cytochrome b558 of the NADPH oxidase complex, is localized on the X-chromosome. Genetic defects in CYBB are responsible for the disease in the majority of male CGD patients. CGD is associated with the development of granulomatous reactions in the skin, lungs, bones, and lymph nodes, and chronic infections may be seen in the liver, gastrointestinal tract, brain, and eyes. There is usually a history of repeated infections, including inflammation of the lymph glands, skin infections, and pneumonia. There may also be a persistent runny nose, inflammation of the skin, and inflammation of the mucous membranes of the mouth. Gastrointestinal problems can also occur, including diarrhea, abdominal pain, and perianal abscesses. Infection of the bones, brain abscesses, obstruction of the genitourinary tract and/or gastrointestinal tract due to the formation of granulomatous tissue, and delayed growth are also symptomatic of CGD. The prevention of infectious complications in patients with CGD involves targeted prophylaxis against opportunistic microorganisms such as Staphylococcus aureus, Klebsiella spp., Salmonella spp. and Aspergillus spp. In this review, we provide an update on organ involvement and the association with specific isolated microorganisms in CGD patients.
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PMID:Common Infections and Target Organs Associated with Chronic Granulomatous Disease in Iran. 3090 13