Efficacy And Tolerability Of Oral Iron Chelator, Deferasirox.

BACKGROUND: Thalassemia major is the severe form of ß thalassemia characterized by severe anaemia, hepatosplenomegaly and facioskeletal changes due to increased haemolysis of defective red blood cells. In iron overload states, high levels of iron exceed the iron-carrying capacity of transferrin within the plasma, leading to the formation of nontransferrin-bound iron form. These nontransferrin-bound iron forms can be taken up into cells, including liver, heart, and endocrine cells leading to organ damage. To prevent complications associated with hemosiderosis, iron chelation therapy remains one of the main objectives of clinical management of the patients affected by Thalassemia Major. METHODS: Thirty-seven patients were enrolled using non randomized convenience sampling technique after the written consent from patients. Patients age 2-30 years were enrolled in this study. Serum Ferritin, ALT, Serum Creatinine were checked at the start of the study, 3 months, 6months and then at the end of the study, i.e., at 9 months of the commencement of the study. They were also assessed for other side effects pertaining to oral tolerability of the drug like vomiting, nausea, GI upset, diarrhoea, urinary complaints or any other subjective complaint. RESULTS: Of the 37 patients, 20 were male (54.1%) and 17 were female (45.9%). Mean age of the patients was 10.2 years (Min. 3 years, Max 21 years). The average serum Ferritin at baseline was noted as 3440 which increased after a period of 3 months, 6 months and 9 months with average of 3359, 3677 and 4394 respectively. After the period of 9 months largest 95% confidence interval of serum Ferritin levels was observed in the range of 3420.17 to 5368.63. In our study, 17 patients required alternative chelation (46%). These patients needed IV Deferioxamine because of the rising trend of Serum Ferritin after the study. CONCLUSIONS: From the results of our study, we infer that oral Deferasirox is not an effective iron chelator. If the patients are taking oral deferasirox, their Serum Ferritin should be checked 3 monthlies. The drug is effective only in maintaining Serum Ferritin levels with levels less than 1500ng/ml. Intravenous Deferioxamine still should be preferred over oral iron chelators for effective control of iron overload and its complications.

ATP7B Mutation Analysis: Wilson Disease, A Difficult to Diagnose Case.

Wilson's Disease (WD) is a common metabolic disorder predominantly involving liver, brain, and eyes. Pancreatic, renal, psychiatric, and cardiac involvement have also been described. No single investigation can be considered diagnostic of WD; therefore, diagnosis is based upon a series of tests best interpreted using Wilson disease diagnostic index (WDDI). We present a difficult-to-diagnose, 9-year girl of consanguineous parents, with chronic liver disease and portal hypertension. Initial workup was equivocal with significantly low serum ceruloplasmin, normal urinary copper excretion and absent Kaiyser-Fleischer (KF) rings. Diagnosis was established by ATP7B mutation analysis. The patient was found homozygous for c.3955C>T (p.Arg1319Ter) in exon 19, a rare mutation described in literature, which results in premature truncation of peptide chain. Key Words: ATP7B, Wilson disease, Copper, Mutations, Hepatolenticular degeneration.

Emerging Antimicrobial Resistance in Neonatal Sepsis.

OBJECTIVE: To determine the frequency and antimicrobial sensitivity pattern of microbial agents causing neonatal sepsis. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Neonatal ICU, Fauji Foundation Hospital, Rawalpindi; Foundation University, Islabambad, from May 2017 to April 2019. METHODOLOGY: Data of all neonates admitted with sepsis during study period was retrieved from computer database. Age at admission, gender, duration of hospital stay and culture reports were recorded. Culture positive patients were further analysed regarding their antibiotic sensitivity. RESULTS: A total of 1,070 neonates, male:female = 1.36:1, mostly newborn, were included in the study. Total mortality was 182 (17%). Blood culture was positive in 79 (7.4%). Gram positive organisms were identified in 37 (46.8%) Staphylococci in 29 (36.7%), Enterococci 7 (8.9%), Corynebacterium species in 1 (1.3%). Gram negative were isolated in 42 (53.2%) Acinetobacter Baumanni in 14 (17.7%), Klebsiella in 12 (15.2%), Enterobacter spp. In 7 (8.8%), E.coli in 5 (6.3%), Pseudomonas in 2 (2.5%) and Proteus in 1 (1.3%) and Serratia in 1 (1.3%) each. Sensitivity pattern of Gram positive organisms was: vancomycin 30/37 (81.1%), ciprofloxacin 13/37 (35.1%) and Gentimicin 12/37 (32.4%). Gram negative organisms sensitivity pattern was: meropenem 12/42 (28.6%), chloramphenical 10/42 (23.8%), gentimicin 6/42 (14.3%), ciprofloxacin 5/42 (11.9%). Highly resistant strains of Klebsiella (13/14) and Acinitobacter (5/12) were sensitive to colomycin only. CONCLUSION: Common organisms responsible for neonatal sepsis were Styphylococci, Acinitobacter, Klebsiella and E.Coli. Gram positive organisms showed sensitivity to vancomycin and gentamicin. Gram negative organisms were highly sensitive to colomycin. Key Words: Neonatolgy, Neonatal sepsis, Antimicrobial sensitivity, Neonatal mortality.

A Novel Clinico-Biochemical Score for Screening of Inherited Metabolic Diseases in Children.

OBJECTIVE: To evaluate a novel clinico-biochemical score for screening of inherited metabolic diseases (IMDs) in children in our setup. STUDY DESIGN: Descriptive analytical study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from August 2016 to August 2017. METHODOLOGY: Clinical data, preliminary biochemical investigations, plasma amino acid (PAA) and organic acid profiles (where indicated) of 354 children, aged <1 year to 12 years, referred to the study place for evaluation of suspected inherited metabolic diseases, was collected and evaluated. A clinico-biochemical score card named Rawalpindi Inherited Metabolic Diseases Score (RISc) was devised, on a scale from 1 to 10, incorporating 5 clinical and 5 important biochemical findings, and each variable was assigned a score, based on its relative frequency/risk. Each case was then assigned the RISc score and evaluated for presence or absence of any inherited metabolic disease, based on the score. This score was validated keeping plasma amino acids and organic acid profiles (in selected cases) as reference standard. RESULTS: Patients were divided into three groups, based on RISc score as low RISc (0.5-2.5), medium RISc (3.0-5.5) and high RISc (6-10). A total of 354 cases reported in 2016 and 2017 and 33 (9.3%) were diagnosed to be having IMDs. One (3.0%) patient from low RISc, four (12.1%) from medium RISc, and 28 (84.8%) from high RISc group were found to test positive for any one IMD. High RISc group had a statistically significant higher IMD rate than the other two groups (p<0.001). Specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value and accuracy were 93%, 85%, 11.8, 0.16, 55%, 98% and 90%, respectively. CONCLUSION: The cost effective RISc, based on clinical data and preliminary biochemical investigations, is highly accurate in diagnosing IMDs in cost restrained setups. It is strongly suggested that the initial screening for suspected IMDs and decision for advanced laboratory testing be carried out, based on the RISc card presented in the study.

Caudal Regression Syndrome with Bilateral Microtia.

Caudal regression syndrome (CRS) is a very rare and unusual disorder affecting the lower part of the body along with multiple systems'involvement. It is mostly found in association with maternal diabetes mellitus during pregnancy; but there is a rare familial form of the disorder, as well. We describe a newborn who presented with the classic clinical and radiologic features of CRS along with bilateral microtia. Our search of the available English language literature did not reveal any such association of CRS with microtia.

CONGENITAL MALARIA.

Neonates with congenital malaria may present with non-specific signs and symptoms which may be mistaken for neonatal sepsis and inborn error of metabolism resulting in delay of diagnosis.and significant mortality and morbidity. Here we present a unique case of 25 days old premature female baby who was diagnosed to have mixed malarial infection. Despite standard treatment the patient was not responding well and was also diagnosed to have congenital adrenal hyperplasia.