Expanding the Genetic Spectrum of AGXT Gene Variants in Egyptian Patients with Primary Hyperoxaluria Type I.

Introduction: Approximately 80% of primary hyperoxaluria cases are caused by primary hyperoxaluria type 1 (PH1, OMIM# 259900), which is characterized by pathogenic variants in the AGXT gene, resulting in deficiency of the liver-specific enzyme alanine-glyoxylate aminotransferase (AGT). This leads to increased production of oxalate, which cannot be effectively eliminated from the body, resulting in its accumulation primarily in the kidneys and other organs. Subjects and Methods: This study included 17 PH1 Egyptian patients from 12 unrelated families, recruited from the Inherited Kidney Disease Outpatient Clinic and the Dialysis Units, Cairo University Hospitals, during the period from January 2018 to December 2019, aiming to identify the pathogenic variants in the AGXT gene. Results: Six different variants were detected. These included three frameshift and three missense variants, all found in homozygosity within the respective families. The most common variant was c.121G>A;p.(Gly41Arg) detected in four families, followed by c.725dup;p.(Asp243GlyfsTer12) in three families, c.33dup;p.(Lys12Glnfs156) in two families, and c.731T >C;p.(Ile244Thr), c.33delC;p.(Lys12Argfs34), and c.568G>A;p.(Gly190Arg) detected in one family each. Conclusion: Consanguineous Egyptian families with history of renal stones or renal disease suspicious of primary hyperoxaluria should undergo AGXT genetic sequencing, specifically targeting exons 1 and 7, as variants in these two exons account for >75% of disease-causing variants in Egyptian patients with confirmed PH1.

Role of Krebs von den Lungen-6 (KL-6) in Assessing Hypersensitivity Pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an increasingly recognized form of diffuse parenchymal lung disease. Krebs von den Lungen-6 (KL-6) is now classified as a human MUC1 mucin protein, and regenerating type II pneumocytes are the primary cellular source of KL-6/MUC1 in the affected lungs of patients with interstitial lung diseases (ILD). Serum KL-6/MUC1 levels have been demonstrated to be useful for the evaluation of various ILD. To determine the role of circulating KL-6 in evaluating the disease activity and management of HP. METHODS: An observational cross-sectional study was conducted on 51 patients with HP and 20 healthy controls. Serum KL-6 levels were measured in both groups. Patients were further assessed based on chest high-resolution computed tomography (HRCT), pulmonary function test, 6-minute walk test, echocardiography, bronchioalveolar lavage, and/or transbronchial biopsy. Patients were divided into the fibrotic and non-fibrotic groups according to the HRCT findings. RESULTS: The median serum KL-6 levels were significantly higher in HP patients as compared to the control group. The median serum KL-6 levels were found to be higher in the non-fibrotic HP group (1,900 IU/mL) as compared to the fibrotic group (1,200 IU/mL). There was a significant inverse correlation between serum KL-6 serum level and the dose of steroids as well as the duration of steroid therapy. CONCLUSION: The presence of higher KL-6 levels in the non-fibrotic HP group implies its enhanced production by regenerating pneumocytes in response to alveolar injury. The significant association between serum KL-6 levels and the dose and the duration of steroid therapy emphasizes the significant role of steroids in the stabilization of the disease.