First patient in the Iranian Registry with novel DOCK2 gene mutation, presenting with skeletal tuberculosis, and review of literature

Background Dedicator of cytokinesis 2 (DOCK2) deficiency is an inborn error of immunity characterized by cellular and humoral immunological abnormalities leading to early-onset infections. Case presentation We reported a novel case of a 27 months old girl presenting with recurrent pneumonia and a history of skeletal tuberculosis at the age of 19-month-old. Her immunological workup revealed persistent lymphopenia and low CD4 + T cell count along with elevated levels of CD19 +, CD20 +, CD16 +, and CD56 + cells. Furthermore, she had a high level of immunoglobulin (Ig) E and a slightly reduced IgM level with a non-protective antibody titer against diphtheria. The whole-exome sequencing (WES) analysis identified a homozygous frameshift deletion mutation (c.1512delG, p.I505Sfs*28) in exon 16 of the DOCK2 gene. We also conducted electronic searches in PubMed, Web of Science, and Scopus databases and reviewed the articles reporting patients with DOCK2 deficiency. The literature search yielded 14 DOCK2-deficient patients suffering from both cellular and humoral immune defects leading to early-onset infections, particularly human herpesvirus (HHV) infection. Conclusion DOCK2 deficiency should be considered in the context of severe or unusual early-onset infections, especially HHV infections, in a patient with a probable clinical diagnosis of combined immunodeficiency. We also recommended that DOCK2-deficient patients might benefit from T-cell receptor excision circle (TREC) assay as part of the routine newborn screening program.

Identification of Lipid Biomarkers for Skeletal Tuberculosis Using an Untargeted Metabolomics Approach

BackgroundThe identification of novel biomarkers in the human body is urgently needed to improve diagnosis and the clinical management of skeletal tuberculosis (STB). This study aimed to identify potential lipid markers to differentiate Mycobacterium tuberculosis infection from other infections, and establish a metabolite biomarker panel suitable for STB diagnosis from abscess samples.MethodsParticipants were recruited from Beijing Chest Hospital between January 2018 and December 2019. Abscess specimens were collected from STB patients and patients diagnosed with other skeletal infections. Then we comparatively explored the lipid metabolomes of abscess specimens from STB and non-STB patients using untargeted lipid metabolomics approach.ResultsA total of 957 features in ESI + mode and 584 in ESI– mode were extracted from the lipidomic data. Among 1541 lipid metabolites, 55 lipid metabolites were significantly changed in STB patients compared to the control group. Significant up-regulation was clearly visualized in phosphatidylethanolamine, phosphatidylinositol, lysophatidylinositols, lysophosphatidylcholines and lysophosphatidylethanolamine. Concomitantly, triacylglycerols and phosphatidylcholines were significantly down-regulated in patients affected by STB. It is worth noting that the two down-regulated monoacyl chain phosphatidylcholine, triacylglycerols and one up-regulated LPE showed excellent diagnostic potential, the AUC values of which were higher than 0.9 and the highest value was 1.0. ConclusionsTo conclude, our data firstly characterize the lipid signatures of abscess specimens from STB patients. The LPEs are significantly upregulated in the STB cases than those in non-STB control, whereas phosphocholines and triacylglycerol are markedly downregulated in the STB cases. The panel of five lipid biomarkers exhibits great capacity for differential diagnosis of STB and non-TB cases.

Tuberculosis, a great masquerader: A case series unveiling rare sites of musculoskeletal involvement through imaging

Skeletal tubercular infections that do not involve the spine or large joints are rarely encountered. This case series aims to highlight the importance of imaging in diagnosing skeletal tuberculosis (TB) at uncommon sites in clinically unsuspected patients by demonstrating specific imaging findings. We present the clinical details and imaging findings of seven pathologically confirmed cases of extraspinal skeletal TB. A multimodality imaging approach including radiography, ultrasonography (USG) and computed tomography (CT) scan was used in most cases. The imaging studies revealed an infective soft tissue collection over different sites including the sternoclavicular joint, acromion process, chest wall and temporo-mandibular joint, along with destruction and erosion of the underlying or adjacent bones. In tubercular endemic countries, strong clinical suspicion should be entertained in cases presenting with a soft tissue collection, even around unusual skeletal sites.