X-linked agammaglobulinemia - first case with bruton tyrosine kinase mutation from Pakistan

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency with more than 600 mutations in Bruton tyrosine kinase (Bkt) gene which are responsible for early-onset agammaglobulinemia and repeated infections. Herein we present a case of a 3-year-old boy with history of repeated diarrhoea and an episode of meningoencephalitis with hemiplegia. The workup showed extremely low levels of immunoglobulin with low CD+19 cells. Genetic analysis showed Btk mutation 18 c.1883delCp.T628fs. To the best of our knowledge this is the first report of a case of XLA confirmed by molecular technique from Pakistan

Societal preferences for gender of surgeons: A cross-sectional study in the general population of Pakistan

Background: Sociocultural norms and gender biases may result in surgeon gender preferences among the general public. This study aimed to understand preferences and perceptions related to surgeon gender among the general population in Pakistan, a lower-middle-income country.Methods: A cross-sectional study was conducted by the Aga Khan University, Karachi, among the adult general population in Pakistan. Sequential mixed-mode data collection was performed via online dissemination on social media platforms and in-person surveying at different geographic locations in Karachi.Results: Among 1604 respondents, 50% did not report having surgeon gender preferences in general. Among respondents with gender preferences, there was a highly significant preference for gender concordance across all surgical subspecialties (p Conclusion: While around half of respondents do not have gender preferences, a significant proportion prefers a gender concordant surgeon across subspecialties. In a society where conservative sociocultural norms play a significant role when seeking health care, this makes yet another compelling argument for gender parity in surgery

The spectrum of primary immunodeficiencies at a tertiary care hospital in Pakistan

Background: Primary Immunodeficiency Disorders (PIDs) are well-known disorders in the West. but the recognition and diagnosis of these disorders is challenging in developing countries. We present the spectrum of PIDs seen at a tertiary care center in Pakistan, identified using clinical case definitions and molecular methods.Methods: A retrospective chart review of children suspected to have PID was conducted at the Aga Khan University Hospital (AKUH) Karachi, Pakistan from 2010 to 2016. Data on demographics, clinical features, family history of consanguinity, sibling death, details of laboratory workup done for PID and molecular tests targeted panel next generation sequencing (NGS) or whole exome sequencing (WES) performed at the Geha laboratory at Boston Children\u27s Hospital, USA was collected. The study was exempted from the Ethical Review Committee of AKUH.Results: A total of 43 children visited the hospital with suspected PID during the study period. Genetic testing was performed in 31/43 (72.1%) children. A confirmed diagnosis of PID was established in 20/43 (46.5%) children. A pathogenic gene variant was identified in 17(85%) of the 20 confirmed cases (Table 1). Twelve (60%) of the confirmed cases of PID were male. The most common presenting symptom was recurrent diarrhea 11/20 (55%). The mean (±S.D) age of the cases at the time of diagnosis was 4.2 (±4.1) years. Chronic granulomatous disease (CGD) was the most common 6/20 (30%) disorder, followed by severe combined immunodeficiency (SCID) 3/20 (15%), leukocyte adhesion deficiency (LAD) 3/20 (15%), agammaglobulinemia/hypogammaglobulinemia 3/20 (15%), and Hermansky-Pudlak Syndrome (HPS) 2/20 (10%). Wiskott-Aldrich Syndrome, Immunodeficiency Centromeric Instability and Facial Anomalies Syndrome (ICF 2), Trichohepatoenteric syndrome (TRES), and C3 deficiency were each diagnosed once {1/20 (4.3%) each} (Table 1). Of these 20 confirmed cases, almost all 19/20 (95%) had a family history of consanguinity. Sibling death was reported in 5/20 (25%) of these cases. Five out of the 20 (25%) children died over the 7-year period for various reasons.Conclusion: PIDs are not uncommon in Pakistan; their diagnosis may be missed or delayed due to the overlapping of clinical features of PID with other diseases and a lack of diagnostic facilities. There is a need to build capacity for early recognition and diagnosis of PIDs to decrease morbidity and mortality

A Novel Nonsense Mutation in FERMT3 Causes LAD-III in a Pakistani Family

Leukocyte adhesion deficiency-III (LAD3) is an extremely rare primary immunodeficiency disorder, transmitted with autosomal-recessive inheritance. It is caused by genetic alteration in the FERMT3 gene, which leads to abnormal expression of kindlin-3. This cytoplasmic protein is highly expressed in leukocytes and platelets, and acts as an important regulator of integrin activation. LAD3 has features like bleeding syndrome of Glanzmann-type and leukocyte adhesion deficiency. FERMT3 mutation(s) have not been well characterized in Pakistani patients with LAD3. In this study, an infant and his family of Pakistani origin, presenting with clinical features of LAD, were investigated to determine the underlying genetic defect. Targeted next generation sequencing (TGS) and Sanger sequencing were performed to identify and confirm the causative mutations, respectively, and their segregation within the family. A novel, homozygous FERMT3 nonsense mutation (c.286C > T, p.Q96∗) was found in the proband, and its co-segregation with LAD3 phenotype within the family was consistent with an autosomal recessive inheritance. Both parents were carriers of the same mutation. This family was offered prenatal diagnosis during first trimester of the subsequent pregnancy; the fetus carried the variant. In conclusion, our study is the first report to identify the novel homozygous variant c.286C > T, p.Q96∗in the FERMT3 gene, which might be the causative mutation for LAD3 patients of Pakistani origin

Experience of Pediatric Rapid Response Team in a Tertiary Care Hospital in Pakistan

Objective: To report our experience before and after implementation of pediatric rapid response team (RRT) in pediatric wards of a tertiary care hospital in Pakistan. Methods: An audit of RRT activity from December 2007 to August 2008 was conducted and reviewed Patient diagnoses at the time of call placement, interventions done and post-intervention clinical outcomes. Clinical Outcomes in the nine months before RRT implementation were compared with those in the first operational nine months after RRT. Results: Eighty-three calls were generated during the post-intervention study period of 9-month (21 calls/1000 admissions). The median age of Patients was 27 months, 37% calls were for infants. The majority of Patients were under care of medical services (93% vs 7% under care of surgical services). Greater numbers of calls were made during 0800-1600 hours (45%). Respiratory issues were the most common reason for activation of RRT. Because of early interventions, majority (61%) of Patients avoided unnecessary PICU stay and expenditure, only 17% required mechanical ventilation in PICU. The code rate per 1000 admissions decreased from 5.2 (pre-RRT) to 2.7 (post-RRT) (p=0.08, OR 1.88(95% CI 0.9 -3.93). The mortality rate of Patients admitted in PICU from wards decreased from 50% to 15% (p=0.25, OR 1.64 (95% CI 0.63 -4.29). Conclusion: Our experience with implementation of RRT was associated with reduction in cardiorespiratory arrest, mortality and saved a lot of PICU resource utilization. It is an excellent Patient-safety initiative especially in resource-constrained countries by bringing PICU reflexes outside the PICU