Beta-Thalassemia Intermedia: A Single Thalassemia Center Experience from Northeastern Iraq

Abstract

Objective. To determine the molecular characterization and disease-associated complications of beta-thalassemia intermedia (β-TI) patients in Sulaymaniyah province, northeastern Iraq. Methods. A total of 159 β-TI patients from 114 families were enrolled. Detection of β-thalassemia mutations was done by reverse hybridization technique and direct gene sequencing. Also, the clinical and hematological data were collected through an electronic-based medical recording system using a designed comprehensive questionnaire. Results. Nineteen different β-globin gene mutations arranged in 37 various genotypes were determined. The most frequent were IVS-II-I (G>A) (47.2%), followed by IVS-I-6 (T>C) (23.3%) and IVS-I-110 (G>A) (5%). Among disease-related morbidities documented, bone disease amounted to 53% (facial deformity and osteoporosis), followed by endocrinopathies 17.6% (growth retardation and subclinical hypothyroidism), cholelithiasis 13.8%, pulmonary hypertension 11.3%, and abnormal liver function test 7.5%, whereas venous thrombosis, extramedullary hemopoiesis, and leg ulcer were less frequently observed. Age≥35 and female sex were risk factors for cholelithiasis, while age was an independent risk for hypothyroidism and female sex was associated with increased risk for osteoporosis. Mean serum ferritin of ≥1000 μg/L was associated with an increased risk of osteoporosis, whereas chelation therapy was protective for a multitude of other complications. Transfusion, on the other hand, increased the risk of osteoporosis, yet it was protective for cholelithiasis and hypothyroidism. Moreover, splenectomy was protective for cholelithiasis, although it was an independent risk for hypothyroidism. Finally, hydroxyurea was associated with an increased risk of osteoporosis, while it was protective for cholelithiasis. Discussion and Conclusion. β+-thalassemia mutation had contributed to 41.25 of families with a less severe β-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of β-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.

Evaluate IL-10 level and gene polymorphism in β-Thalassemia patients with related to microbial infection and disease outcome

“…This result agree with (Ali and Abdulla., 2020) who found that male recorded 94(54%) and 81(46%) were females with a ratio 1.2: 1and mean age of patients were (10.5 ±5.8 years) , the range age of patients from 5 months to 34 years and found that more than half (55%) between aged 1 -10 years. In study by Amin et al, (2020)confirmed that male more susceptible to β-thalassemia disease with frequency 56.6% males and 43.4% females, with ratio male : female ratio of 1.3 : 1. The patients' ages ranged between 1.4 -54 years with a median of 15 yrs.…”

The spectrum of beta-thalassemia mutations in the 22 Arab countries: a systematic review

“…Although the spectrum of β-thal mutations in the Arab region is highly diversified and mostly shared with other ethnic groups, we identified six HBB gene mutations that our search strategy identified as unique to Arabs ( Table 1) is associated with both β-thal intermedia and major in Iran [61], as well as in Saudi Arabia and Palestine [52,51], while it causes β-thal major in United Arab Emirates, Syria, Lebanon, Algeria and Qatar [54,59,50,53,45], and it is linked with β-thal intermedia in Iraq and Kuwait [21,55]. The c.27dupG is associated with β-thal major in Saudi, Syria, Qatar [58,22,45], while in Iraq it causes β-thal intermedia and it is associated with both β-thal intermedia and major in Palestine, Egypt [44,23].…”

Genetic epidemiology of hemoglobinopathies among Iraqi Kurds

“…It also shows that the bulk of the mutations was Mediterranean, with some Turkish, Kurdish, Saudi Arabian, Azerbaijani, and Asian Indian origins. A further 15 mutations were reported infrequently or sporadically (< 1.0%) that include codon 36/37 (−T), IVS-I-130 (G>C), IVS-II-745 (C>G), IVS-II-850 (G>T), codon 22 (−7 bp), codon 30 (G>C), codon 15 (G>A), codon 127 (CAG>CGG), − 101 (C>T), − 87 (C>G), − 30 (T>A), − 28 (A>C), poly-A (AATAAA>AATAAG), 5′ UTR + 22 (G>A), and CAP + 1(A>C) (Al-Allawi et al 2010a, 2014Amin et al 2020;Jalal et al 2010;Shamoon et al 2015). The spectrum of mutations noted among Kurds is quite consistent with their history and interactions with surrounding Mediterranean populations, while the presence of Asian Indian mutations could be attributed to the region being along the ancient silk road route, which connected China and Europe through the Indian subcontinent and the Middle East.…”