RESUMEN
Background: Cystic fibrosis (CF) is a multisystemic chronic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. These mutations are classified in to six classes. Ivacaftor is a CFTR potentiator which partially restores the CFTR function for class III mutations. In Oman, p.Ser549Arg (class III) is the most common mutation (65% of cases). Our study prospectively evaluated the tolerance and clinical efficacy of ivacaftor. Methods: A prospective observational study was conducted at the Royal Hospital, Oman. All children aged 6-18 years who are followed and carry at least one copy of the p.Ser549Arg mutation were started on Ivacaftor and included in the study. Data collected included weight, height, forced expiratory volume in first second (FEV1), sweat chloride concentration, stool elastase level and liver enzymes at baseline and at 12, 24, 36, and 48 weeks after initiation of treatment. The number of CF pulmonary exacerbations one year before and during treatment were compared. Results: Twenty one children were started on Ivacaftor (90% homozygous for p.Ser549Arg). The mean age was 10.8 (SD ±3.5) years. When compared to baseline, FEV1 significantly improved by a mean of 10.8 (SD ±13.5) percentage points (pp) and 14.3 (SD ±7.5) pp at 12 and 48 weeks respectively. The sweat chloride level significantly dropped from a mean of 107 (SD ±8.5) mmol/l to 38.5 (SD ±22.3) mmol/l at 12 weeks and remained low. The Body Mass Index (BMI) improved by a mean of 1.37 (SD ±1.3) kg/m 2 and 1.9 (SD ±1.35) kg/m 2 at 24 and 48 weeks of treatment respectively. The number of admissions the year before and during treatment reduced significantly from a mean of 2.2 (SD± 1.9) to 0.7 (SD ±1) admission per year. Two children developed transaminitis. Conclusion: Ivacaftor is well tolerated and resulted in a significant improvement in FEV1, BMI and sweat chloride level in children with p.Ser549Arg CFTR mutation.
RESUMEN
Objectives: To describe the demographic distribution of cystic fibrosis (CF) in Omani children, estimate the national prevalence, and provide updated mutational panels of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Methods: We conducted a retrospective cross-sectional study of all CF patients who had been diagnosed and followed-up at Sultan Qaboos University Hospital and Royal Hospital in Oman between 2006 and 2020. Data were collected from electronic hospital records and telephone interviews. Results: A total of 227 patients with CF were included in the study. Geographical clusters of the disease were identified in the governorates of Al-Batinah, A'Dhahirah, and A'Dakhiliyah. Parental consanguinity and family history of CF were present in 68.3% and 69.6% of the patients, respectively. The most common CFTR mutation was p.Ser549Arg (52.0%), followed by p.Phe508del (12.3%), and c.2988+1G>A (4.4%). Three novel CFTR mutations were identified, viz., Leu88TyrFs*, p.Asp192Val, and c.4242+1G>C. Conclusions: The estimated prevalence of CF in Oman is 10.3 per 100 000 individuals. Premarital genetic counseling and preimplantation genetic testing are recommended in CF-prevalent regions.
RESUMEN
Mutations in lipopolysaccharide-responsive vesicle trafficking, beach and anchor-containing protein (LRBA) cause immune deficiency and inflammation. Here, we are reporting a novel homozygous mutation in LRBA allele in 7-year-old Omani boy, born to consanguineous parents. He presented with type 1 diabetes, autoimmune haematological cytopenia, recurrent chest infections and lymphocytic interstitial lung disease. The patient was treated with CTLA4-Ig (abatacept) with good outcome every 2 weeks for a period of 3 months. He developed complete IgG deficiency, but remarkably, histological examination revealed germinal centres and plasma cells in lymphoid and inflamed lung tissue. Further charatecterisation showed these cells to express IgM but not IgG. This ex vivo analysis suggests that LRBA mutation confers a defect in class switching despite plasma cell formation.