Establishing biotinidase reference interval: A foundation stone for newborn screening of biotinidase deficiency in Pakistan.

OBJECTIVE: To determine the reference interval of biotinidase activity in healthy neonates. METHODS: The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from May to November 2019, and comprised blood samples collected from healthy neonates aged 2-6 days. The samples were collected on filter paper and analysed on genetic screening processor based on dissociation-enhanced lanthanide flouroimmunoassay. Data was analysed using SPSS 21. RESULTS: Of the 120 dried blood spot specimens, 81(67.5%) were from male babies and 39(32.5%) from female babies. Reference interval for biotinidase activity, based on 2.5th and 97.5th percentiles, was from 3.0 to 11.0 nmol/ml/min. CONCLUSIONS: Screening of newborns for biotinidase deficiency is crucial to prevent irreversible neurological damage.

Association of Serum Hyaluronic Acid and Laminin with Polymerase Chain Reaction Findings in Hepatitis C Patients.

OBJECTIVES: To find the association of serum hyaluronic acid and laminin levels with polymerase chain reaction (PCR) results in hepatitis C sero-positive patients; and the correlation among viral load, serum hyaluronic acid, and serum laminin levels. STUDY DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan from December 2019 to July 2020. METHODOLOGY: One hundred and eighty diagnosed cases of hepatitis C patients were included in this study. To find association, cross tabulation was done after dividing into two groups according to their median by applying Chi-square test. Correlation of viral load, duration of disease, serum hyaluronic acid and laminin levels were calculated using Spearman's correlation. RESULTS: There were 124 (68.9%) males and 56 (31.1%) females. Median (IQR) age was 36 (32.3 - 45.0) years; while median duration of disease was 12 (8 - 18) months. There was a strong association between PCR positive cases with hyaluronic acid (p <0.001) and serum laminin levels (p <0.001). A strong relationship was found between viral load and serum hyaluronic acid (r =0.889, p <0.001), as well as with serum laminin (r =0.889, p <0.001). CONCLUSION: Current study established a strong significant association between PCR results and disease duration with levels of serum laminin and hyaluronic acid. The levels of serum laminin and serum hyaluronic acid also correlate well with viral load and duration of disease. Key Words: Hepatitis C, Hepatic fibrosis, Hyaluronic acid, Laminin.

Rare bleeding disorders: spectrum of disease and clinical manifestations in the Pakistani population.

BACKGROUND: Rare inherited coagulation factor deficiencies constitute an important group of bleeding disorders. A higher frequency of these disorders is seen in areas of high consanguinity. Our aim was to study the prevalence and spectrum of rare inherited bleeding disorders, characterize the severity of the deficiencies, identify different clinical manifestations, and evaluate different treatments provided. METHODS: This cross-sectional study was conducted in the Department of Haematology, Armed Forces Institute of Pathology Rawalpindi, between January 2014 and December 2018. A detailed history was taken, and an examination was performed. The signs and symptoms were noted, and the patients were diagnosed on the basis of a coagulation profile. The disease severity was assessed using factor assays. RESULTS: Among 2,516 patients with suspected coagulation disorders, 774 (30.8%) had an inherited bleeding disorder. Of the 774 patients, 165 (21.3%) had a rare bleeding disorder; 91 (55.2%) of them were males, and 74 (44.9%) were females, with a male-to-female ratio of 1.2:1. The median patient age was 9 years 3 months. The most common disorder was factor VII deficiency (46 patients, 27.9%). The most common clinical presentation was bruising in 102 (61.8%) and gum bleeding in 91 (55.2%) patients. CONCLUSION: The most common rare bleeding disorder in our population is factor VII deficiency. The prevalence of these bleeding disorders is high in our population due to a high number of consanguineous marriages.

Comparison of Estimated Glomerular Filtration Rate with Both Serum Creatinine and Cystatin C (eGFRcr-cys) versus Single Analyte (eGFRcr or eGFRcys) Using CKD-EPI and MDRD Equations in Tertiary Care Hospital Settings.

OBJECTIVES: To assess and compare the glomerular filtration rate (eGFR) estimated through MDRD and CKD-EPIcr equations in early and late stages of chronic kidney disease on biochemical marker creatinine (eGFRcr), cystatin C (eGFRcys); and combined (eGFRcr-cys), using CKD-EPI equation. STUDY DESIGN: Observational, comparative cross-sectional study. PLACE AND DURATION OF STUDY: Chemical Pathology and Endocrinology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi in collaboration with Armed Forces Institute of Urology (AFIU), Rawalpindi from October 2019 to March 2020. METHODOLOGY: GFR was assessed on the basis of creatinine clearance taking serum and 24-hour urinary specimens. MDRD and CKD-EPI equations were applied to calculate eGFR by serum creatinine (eGFRcr), cystatin C (eGFRcys), and combined (eGFRcr-cys). Pearson correlation technique was used to compare eGFR calculated by different equations with creatinine clearance in different stages of CKD. Performance of equations was evaluated and compared in different stage of CKD. RESULTS: A total of 181 subjects were enrolled. Median age was 57 years (IQR, 25). Median (IQR) GFR (ml/min/1.73m2) calculated by CrCl, MDRD, CKD-EPIcr, CKD-EPIcys and CKD-EPIcr-cys equations were 45.1 (41.5), 50.6 (23.8), 52.0 (28.0), 43.0 (65.0) and 45 (47), respectively. eGFR calculated by CKD-EPIcr had positive and slightly higher correlation (r=0.880) than MDRD study equation (r=0.867). While comparing the markers, it was observed that CKD-EPIcys had better correlation in early stages of CKD (r=0.889); whereas, CKD-EPIcr performed better in late stages (r=0.896). CKD-EPIcr-cys had the highest correlation (r=0.984) at all stages of CKD. CONCLUSION: eGFR calculated by CKD-EPI equation considered as better diagnostic efficient response than MDRD equation in diagnosis and staging of chronic kidney disease. While applying CKD-EPI equation for measurement of eGFR, eGFRcr-cys performs better than any of eGFRcr or eGFRcys at all stages of CKD. Key Words: Estimated glomerular filtration rate (eGFR), Cystatin C (Cys), Creatinine (Cr), Creatinine clearance (CrCl), CKD-EPI equation, MDRD equation.

Evaluation of random plasma glucose for assessment of glycaemic control in type 2 diabetes mellitus.

OBJECTIVE: To evaluate the accuracy of random plasma glucose in outpatients with type 2 diabetes mellitus for assessing glycaemic control. METHODS: This comparative, cross-sectional study was conducted at the chemical pathology department of PNS Shifa Hospital, Karachi, from August 2015 to March 2016, and comprised data of subjects with type 2 diabetes mellitus who reported for evaluation of glycaemic control in non-fasting state. All blood samples were analysed for random plasma glucose and glycated haemoglobin. Random plasma glucose was compared as an index test with glycated haemoglobin considering it as reference standard at a value of less than 7% for good glycaemic control. SPSS 20 was used for data analysis. RESULTS: Of the 222 subjects, 93(42%) had good glycaemic control. Random plasma glucose showed strong positive correlation with glycated haemoglobin (p=0.000).Area under curve for random plasma glucose as determined by plotting receiver operating characteristic curve against glycated haemoglobin value of 7% was 0.89 (95% confidence interval: 0.849-0.930). Random plasma glucose at cut-off value of 150 mg/dl was most efficient for ruling out poor glycaemic control among patients with type 2 diabetes mellitus with 90.7% sensitivity and69.9% specificity and Youden's index of 0.606. CONCLUSIONS: Random plasma glucose may be used to reflect glycaemic control in adults with type 2 diabetes mellitus in areas where glycated haemoglobin is not feasible.