Background/Aims: The purpose of this study was to identify the spectrum and frequency of pathogenic variants as well as the clinical and genetic insight of hereditary chronic pancreatitis in ...Pakistani children. Materials and Methods: The deoxyribonucleic acid of affected probands of 44 unrelated Pakistani families, having hereditary chronic pancreatitis-affected children, were subjected to massive parallel sequencing for candidate reported genes (SPINK1, PRSS1, CFTR, CPA1, CTRC, CBS, AGL, PHKB, and LPL). Data were analyzed using different bioinformatics tools for the variants and in-silico analysis. All the identified variants were validated by direct sequencing of the targeted exons in the probands and their parents. Results: There were 50 patients included in this study with confirmed hereditary chronic pancreatitis. Nine known mutations in SPINK1, PRSS1, CFTR, CTRC, CBS, and AGL genes, and 10 novel variants in LPL, CFTR, CTR, and PHKB genes were identified. The identified variants were found in heterozygous, compound heterozygous, and trans-heterozygous forms, with rare allele frequency in the normal population. The novel variants were c.378C>T(p.Lys126Asn) and c.719G>A(p.Arg240Gln) in CTRC, c.586-3C>A and c.763A>G(p.Arg255Gly) in CPA1, c.1160_1161insT(p.Lys387Asnfs*26), c.784C>T(p.Gln262*), c.1139+1G>A, c.175G>A(p.Gly59Arg) in LPL, c.388C>G(p.leu130val) in CFTR, and c.2327G>A(p.Arg776His in PHKB). The phenotypic characteristics were variable and correlated with the relevant variant. Conclusions: The genetic composition plays a significant role in the predisposition of hereditary chronic pancreatitis. The clinical presentation varies with the genetic determinant involved. This information would help in building up a diagnostic algorithm for our population that can be used for genetic screening services in affected cohorts. Keywords: Hereditary pancreatitis, trans-heterozygotes, PRSS1, SPINK1, Pakistan
To explore the spectrum of presentation, underlying monogenetic defects and outcome in very early onset inflammatory bowel disease (VEO-IBD).
The prospective, observational study was conducted at the ...Children's Hospital, Lahore, Pakistan, from January 2017 to December 2018, and comprised children developing features of inflammatory bowel disease aged <6 years. Data included demography, clinical presentation, diagnostic tools and outcome. Data was analysed using SPSS 21.
Of the 60 children with relevant symptoms, 26(43.3%) were diagnosed as having very early onset inflammatory bowel disease. Of them, 13(50%) had underlying monogenic defect, and 16(61.5%) had ulcerative colitis. There were 22(84.6%) males with median age of 1.5(11) months in monogenic inflammatory bowel disease versus 24(43) months for non-monogenic inflammatory bowel disease (p<0.05). In the monogenic group, isolated rectal bleeding was the major presentation 13(100%) versus non-monogenic who presented mainly with failure to thrive 13(100%). Upper and lower endoscopies with histopathology had good diagnostic yield and inflammatory infiltrates on the biopsied tissues were the major findings. Mutations detected among the subjects were XIAP, PRKDC, PIK3CD, RAG-1, LRBA, DOCK8, TTC7, MEFV and EPCAM. Mortality was significantly higher in the monogenic group 7(54%) than in the non-monogenic group 2(15%) (p<0.05).
Very early onset inflammatory bowel disease should be suspected when conventional management fails to rectify common disease mimickers. Testing for underlying immunological defect and genetic mutation would be helpful for managing these rare disorders.
OBJECTIVE: To determine the phenotypic and genotypic characteristics of progressive familial intrahepatic cholestasis (PFIC) type 3 in Pakistani children in a hospital setting. METHODS: This ...cross-sectional observational study was conducted at department of Pediatrics Gastroenterology & Hepatology, The Children’s Hospital Lahore, Pakistan from October 2020 to March 2021. Patients of either sex under 16 years of age presenting with jaundice, pruritus, neonatal cholestasis or with chronic liver and gamma glutamyl transferase >100 IU/ml were included in the study after taking informed consent by parents. For Molecular genetics 2ml blood in EDTA was sent to an international laboratory free of cost on research basis. Reports were assessed and levels were noted and genetic coding was also recorded. Data was entered and analyzed in SPSS version 22. Molecular data was interpreted with the help of clinical geneticist. RESULTS: Out of 34 children, 14 (41.2%) were males and 20 (58.8%) were females. Mean age of children was 6.71±3.10 years. Consanguinity was noted in 32 (94.1%) parents having positive family history in 24 (70.6%) cases. The most common mutation was c. 1783C>T p.(Arg595*), noted in 12 (35.3%) cases, followed by c. 2861G>T p.(Gly954 ASP) 8 (23.5%) cases, c. 153G>A p.(Trp51) 3 (8.8%) cases, c. 1714 C>T p.(Gln572*) c. 1906C>T p. (Gln636), c. 3220G>A p.(Gly1074Arg, c. 3433del p. (val1145Leufsx7) in 2 (5.9%) cases each, c. 3859 C>T p.(1287Argext*) c. 88-91del p.(Lys30gly fsx7) and c. 1429c>T p. (Gln477) in one (2.9%) case each. CONCLUSION: Children with PFIC type 3 have variable phenotypic and genotypic presentation.
Objective: To evaluate the quality of life among children with inflammatory bowel disease (IBD) by the inflammatory bowel disease questionnaire.
Study Design: Cross-sectional study.
Place and ...Duration of the Study: Department of Pediatric Gastroenterology, Children's Hospital and Institution of Child Health, Lahore Pakistan, from Nov 2020 to Apr 2021.
Methodology: A total of 60 cases (Crohn's disease or ulcerative colitis) were enrolled in the study. Quality of life was measured according to the Modified IMPACT-III questionnaire.
Results: There were 38(63.3%) males and 22(36.7%) female children. The mean age was 9.57±3.40 years, while 33(55.0%) children were above ten years. The mean maternal age was found to be 37.10±4.09 years. There were 36(60.0%) children with Crohn's disease, while 24(40.0%) had ulcerative colitis. Children with Crohn's disease were found to have a significantly low quality of life compared to children in the ulcerative colitis group in the social domain (p<0.05). In addition, children with ulcerative colitis had a significantly low quality of life with regard to bowel symptoms (p<0.05).
Conclusion: Overall scores showed a low quality of life among children with IBD. Children with Crohn's disease had significantly low social QoL, while children with ulcerative colitis showed significantly low QoL regarding bowel symptoms.
Background The two commonly used methods for uretero-ileal anastomosis (UIA) during radical cystectomy for muscle-invasive bladder cancer (MIBC) are the Bricker and Wallace 1 techniques. Published ...data on the incidence of strictures at anastomotic sites is limited. This study compares both anastomotic techniques in terms of uretero-ileal stricture (UIS) rates and the factors that govern it in the patient group. Material and methods Records of all patients presenting with bladder cancer who underwent radical cystectomy at the department of uro-oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) Lahore, Pakistan, from January 1, 2009, to December 31, 2018, were reviewed retrospectively, and all adult patients aged >18 years out of them were selected for the study. Results With a total of 116 patients, the mean age was 54.37 ± 11.16 and a male majority (83.6%). Urinary diversion using ileal conduit was performed in 70 (60.3%) patients and the rest of them i.e. 46 (39.7%) had neobladder formation. Amongst them, uretero-ileal anastomosis was constructed via Bricker and Wallace 1 in 73 (62.9%) patients and 43 (37.1%) patients respectively. Pelvic radiotherapy was received by 13 (11.2%) patients. Anastomotic stricture developed in 19 (16.4%) cases. A relatively similar proportion of stricture rate was found in Bricker and Wallace 1 technique (10% vs 13%). Body mass index (BMI) was found to be significantly higher in patients who developed UIS. Incidence of stricture formation was more on the left than right side i.e. 12 (63.2%) vs five (26.3%) while two (10.5%) patients developed bilateral strictures. Conclusion No significant difference in stricture formation was noted between Bricker and Wallace 1 technique. High BMI and anastomotic leaks were the contributory factors for this complication during our experience.
Background: Hepatitis B virus (HBV) is the aetiological agent of transfusion-transmitted hepatitis globally. Beta thalassaemia major individuals are at greater risk of contracting HBV infection due ...to multiple blood transfusions required for the medical management of these patients. Based on HBV genetic variability, it is divided into 10 genotypes. The determination of HBV genotypes has significant implications for clinical management and treatment regimens. Aim: This study was performed to assess the HBV epidemiology and circulating genotypes in multi-transfused β-thalassemia major patients with the aim to be considered while formulating the treatment pattern taking into account particular needs of thalassaemia patients. Materials and Methods: This study was performed from September 2018 to June 2019, at the Department of Pathology and Transfusion Medicine, Shaheed Zulfiqar Ali Bhutto (SZAB) Medical University, Islamabad. A total of 2,260 thalassaemia patients were enrolled in the study. The study was endorsed by the Ethics Committee of the SZAB Medical University, Islamabad. The samples were serologically screened for HBsAg on the LIAISON® XL Murex HBsAg Quant assay (DiaSorin S.p.A., Italy) a chemiluminescence based immunoassay (CLIA). HBV quantitative PCR kit was used to measure the HBV DNA in serum samples. The HBV genotypes were determined using universal primers targeting the P1 and S1 region amplification. Results: Of 2,260 thalassaemia patients, 64.6% were males while 35.4% were females. The HBsAg was identified in 98 individuals (4.33%). The PCR analysis was done for these 98 patients and in this cohort, genotype D was 59.18% (n = 58), genotype A was 21.42% (n = 21) while genotype C was 19.38% (n = 19). Conclusion: The determination of HBV genotypes in the multi-transfused patients is key to the effective management of chronic HBV patients as the severity and course of the disease is dependent on a specific type of genotypes. Quality assured screening of donated blood will prevent the incidence of HBV in thalassaemia patients.
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