Chromosomal Breakage in Fanconi Anemia and Consanguineous Marriages: A Social Dilemma for Developing Countries.

Introduction A clear picture of the prevalence of Fanconi anemia is not known due to limited studies and research of the subject. This study will detect the frequency of positive chromosomal breakage in pediatric aplastic patients and provide the evidence-based guidelines which help in consideration of appropriate treatment and awareness to the society. Methods A total of 104 aplastic anemia patients were recruited of age <18 years whose samples were tested for chromosomal breakage with mitomycin C (MMC). History of consanguinity between parents were documented for all the patients referred to us. Result Out of 104 diagnosed aplastic anemia patients, 35 (33.7%) patients were found to be Fanconi positive. Mean age of all hypoplastic patients for aplastic anemia and Fanconi anemia was 10.7 ± 4.5 and 10.6 ± 3.5, respectively. Male preponderance was found to be higher (64, 61.5%) as compared to females (40, 38.5%) in aplastic patients. The male to female ratio was observed as 2.5:1 in Fanconi patients while 1.3:1 in non-Fanconi aplastic patients. Parental consanguinity was observed in 33 (94.2%) with Fanconi anemia. Conclusion Fanconi anemia accounts for significant number of patients with hypoplastic bone marrow, therefore consanguineous marriages should be avoided through mass education in Pakistan.

Laboratory diagnosis for thalassemia intermedia: Are we there yet?

BACKGROUND: Differentiation between thalassemia major and thalassemia intermedia at presentation is not uniformly characterized, for which an absolute criteria needs to be developed. This study investigated the primary and secondary genetic modifiers to develop a laboratory finding by forming different genetic mutational combinations seen among thalassemia intermedia patients and comparing them with thalassemia major. METHODS: This cross-sectional study analyzed 315 thalassemia intermedia patients. One hundred and five thalassemia major patients were recruited on the basis of documented evidence of diagnosis and were receiving blood transfusion therapy regularly. Various mutational combinations were identified, and comparison was performed between thalassemia intermedia and major using statistical software STATA 11.1. RESULTS: The mean age of the total population was 5.9 ± 5.32 years of which 165 (52%) were males. Of the two groups (thalassemia intermedia and thalassemia major), IVSI-5, IVSI-1, and Fr 8-9 were more prevalent among the thalassemia intermedia cohort. When comparison was performed between the thalassemia intermedia and thalassemia major patients, it showed significant results for the presence of Xmn-1 polymorphism. CONCLUSION: The presence of IVSI-5 homozygous with Xmn-1, IVSI-5 heterozygous with Xmn-1, Cd 30 homozygous with or without Xmn-1 and IVSI-1 homozygous or heterozygous either with or without Xmn-1 prove to be strong indicators towards diagnosis of thalassemia intermedia.

Sensitivity and specificity of single-tube osmotic fragility test and its different methods as screening test for thalassemia trait: an alternative to expensive laboratory tests for resource-limited countries.

OBJECTIVE: To determine the sensitivity and specificity of single-tube osmotic fragility (SOFT) and its different methods as screening test for thalassemia trait. METHODS: A cross-sectional study was conducted at Omair Sana Foundation. A total of 400 participants were included in the study. Three hundred were known thalassemia carriers (parents with at least one child with thalassemia major), while 100 were healthy blood donors. SOFT was performed on all 400 participants. Serum iron, ferritin, and DNA tests were performed on 100 participants (donors). ARMS technique was used for detecting thalassemia mutations. RESULTS: Sensitivity and specificity of SOFT (venous method) were found to be 99.6% and 86%, respectively, while with EDTA method, sensitivity was 95% and specificity was 96%. For venous and EDTA methods, positive predictive values were 95.5% and 98.6%, respectively, while negative predictive values were 98.8% and 86.6%, respectively. Use of EDTA and storage had an effect on the results. Sensitivity of SOFT was 95% at 5 min, while it decreased to 87% with EDTA method at 240 min. Sensitivity of SOFT for iron deficiency anemia was found to be 14%. CONCLUSION: SOFT can be used as screening test for thalassemia trait in a cost-effective way. Moreover, we also found that SOFT should be performed on venous blood without adding preservatives (EDTA) that can interfere with the results.