Association between genotype and disease complications in Egyptian patients with beta thalassemia: A Cross-sectional study

Abstract

In beta thalassemia, the degree of globin chain imbalance is determined by the nature of the mutation of the β-gene. β° refers to the complete absence of production of β-globin on the affected allele. β+ refers to alleles with some residual production of β-globin. The homozygous state results in severe anemia that necessitates regular blood transfusion. On the other hand, frequent blood transfusion can lead to iron overload resulting in progressive dysfunction of the heart, Liver as well as multiple endocrinopathies. We studied the impact of genotype on the development of disease complications in patients with β thalassemia. A Cross sectional study was carried on 73 patients with beta thalassemia. Genotyping was determined by DNA sequencing technique. Routine investigations as well as MRI liver and heart were performed to assess iron overload. We found that β+β+ was the most common genotype in our patients followed by β°β° and β°β+. Mean Liver iron content (LIC) was significantly higher in β°β° compared to β°β+ and β+β+ genotypes and mean cardiac T2* was significantly lower in β°β° compared to β°β+ and β+β+ genotypes. Hepatic complications, hepatitis C, cardiac complications and some endocrinopathies were significantly higher in patients with β°β° genotype compared to other genotypes which explain the role of the underlying genetic defect in thalassemia patients in development of disease complications.

Complications and Challenges in the Management of Iraqi Patients with β-Thalassemia Major: A Single-center Experience

“…The median age of 13 years reported in the current series is not unexpected and is consistent with an earlier study from Iraq which revealed that the bulk of β-TM patients are children or adolescents. 9 It is also consistent with reports from neighboring Iran, Turkey, and Egypt, 10 - 12 though it is much lower than reports from developed countries like France, Italy, and the US. 13 - 15 This is consequent to the higher quality of care and follow-up in the latter countries as opposed to our region.…”

“…Among the transfusion-related infections in β-TM in our series, HCV stands out at 35.3%, which is similar to rates reported from the US (35%), but higher than rates reported from France, Turkey, Lebanon, Egypt, and Iran (4.1–26%), 12 - 14 , 18 - 20 and lower than rates reported from Pakistan (49%). 21 An earlier study from Southern Iraq reported higher rates of HCV seropositivity at 42.5% among transfusion-dependent thalassemia patients, though they noted that the rates are declining progressively.…”

“…10 - 14 , 16 , 18 , 28 , 30 , 31 On the other hand, the rate of hypoparathyoidism at 3.3% is less than the rates reported in some other populations of 4.0–10.5%. 10 , 12 , 14 , 18 , 28 , 30 , 31 Diabetes mellitus is another recognized complication and varies in frequency between 2.1% and 26.7%, so our rate of 3.3% is near the lower end of the range. 10 - 14 , 16 , 18 , 28 , 30 , 31 Hypogonadism is the most frequently reported complication due to iron overload in almost all thalassemic populations in developed and underdeveloped countries and ranges from 28.7% to 73.3%, so our figure of 52.8% is expected.…”

“… 14 Such less than adequate transfusion therapy coupled by lax adherence to timely transfusions by patients/families is reflected by the prominence of skeletal changes (thalassemic faces) noted in more than half of our patients, and the higher than expected frequency of short stature, which was also seen in Egyptian patients. 12 The need to review the locally adopted management guidelines at the thalassemia center and promote adherence to thalassemia international federation most recent guidelines is paramount. 17 Furthermore, steps to better educate patients and their guardians on the need for regular and timely transfusion should be undertaken.…”

Identification of Circulating Endocan-1 and Ether Phospholipids as Biomarkers for Complications in Thalassemia Patients

“…β-thalassemia is a monogenic heritable blood disorder with significant variability in disease progression and success of treatment [29][30][31]. Thus, development of novel therapeutics, ideally matched with precision medicine based upon new biomarkers, is desirable.…”