An unusual cause of granulomatous disease

BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disorder of phagocytic cells caused by an inability to generate active microbicidal oxygen species required kill certain types of fungi and bacteria. This leads to recurrent life-threatening bacterial and fungal infections with tissue granuloma formation. CASE PRESENTATION: We describe a case of X-linked Chronic granulomatous disease (CGD) diagnosed in an 18-year-old male. He initially presented with granulomatous disease mimicking sarcoidosis and was treated with corticosteroids. He subsequently developed Burkholderia cepacia complex pneumonia and further investigation confirmed a diagnosis of CGD. CONCLUSION: Milder phenotypes of CGD are now being recognised. CGD should be considered in patients of any age with granulomatous diseases, especially if there is a history of recurrent or atypical infection

P67-phox (NCF2) Lacking Exons 11 and 12 Is Functionally Active and Leads to an Extremely Late Diagnosis of Chronic Granulomatous Disease (CGD)

Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000+2T→G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage

Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

Assessing immune function in adult bronchiectasis

Bronchiectasis is characterized by chronic airway infection and damage and remains an important health problem. Recent literature has emphasized the role of host defence and immune deficiency in the pathogenesis of bronchiectasis, but there have been few studies of immune function in adult bronchiectasis. A comprehensive screen of immune function was conducted in 103 adult patients with bronchiectasis, encompassing full blood examinations, immunoglobulins and IgG isotypes, complement levels, lymphocyte subsets and neutrophil function. Full blood examinations were normal in this cohort, as were complement levels. Statistical analysis confirmed that a significant number of subjects had low levels of IgG3 (13 patients), B cell lymphocytes (six patients) and T helper cell lymphocytes (seven patients) when compared with controls (P< 0·05). The most common abnormality was found with testing of the neutrophil oxidative burst. All subjects had a normal neutrophil phagocytic function but 33 of the subjects had an oxidative burst that was below the normal range (P< 0001). Almost half the group (45 subjects) had abnormally low levels of one of these four parameters. The findings of low B cells, Th cells and oxidative burst in bronchiectasis are novel. The results emphasize the importance of immune function assessment for adult bronchiectasis

Percutaneous vertebroplasty: a comparison between the procedure using the traditional and the new side-opening cannula for osteoporotic vertebral fracture Vertebroplastia percutânea: uma comparação entre o procedimento usando a cânula tradicional e a nova cânula de orifício lateral para fratura vertebral osteoporótica

A total of 47 percutaneous vertebroplasties (PVs) were performed for osteoporotic vertebral fractures in 31 patients, 25 PVs were performed using the frontal-opening cannula (FOC) and 22 using the new side-opening cannula (SOC), randomly distributed. The incidence of cement extrusion was 27% with the SOC, and 68% with the FOC, all asymptomatic (p<0.01). The pain control was similar for both groups, with good improvement of pain in most of the patients, and there were no clinical relevant complications. The cement leakage can be significantly reduced with this new SOC, which allows for a better cement injection toward the center of the vertebral body, increasing the safety of the procedure, with no increase in cost.<br>Um total de 47 vertebroplastias percutâneas (VP) foram realizadas para fraturas vertebrais osteoporóticas em 31 pacientes, 25 VP foram realizadas usando-se a cânula de orifício frontal (COF) e 22 com a nova cânula de orifício lateral (COL), distribuídos randomicamente. A incidência de extrusão de cimento ortopédico ocorreu em 27% com a COL, e 68% com a COF, todas assintomáticas (p<0,01). O controle da dor foi similar em ambos os grupos, com boa melhora da dor na maioria dos pacientes, sem complicações clínicas relevantes. A extrusão do cimento pode ser significativamente reduzida com esta nova COL, que permite uma melhor injeção do cimento para o centro do corpo vertebral, aumentando a segurança do procedimento, sem aumento no seu custo