RESUMO
BACKGROUND: Iron overload (IO) is a complication in transfusion dependent beta thalassaemia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka. MATERIALS AND METHODS: Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for a period of one year in all. Those who were ≥ 8 years of age (40 patients) underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes. RESULTS: The median age of the patients of this cohort was 10 years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The median level of serum ferritin was 2452 ng/dl. Hepatic IO was seen in 37 (92.5%) patients and cardiac IO was seen in 17 (42.5%) patients. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO. Thirty-two (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. Eight (15.4%) and 1 (1.9%) patients were heterozygotes for pathogenic and likely pathogenic variants of HFE genes respectively. There were no pathogenic variants for the TfR2 and SLC40A1 genes. The heterozygotes of the pathogenic variants of the HFE were not at increased risk of IO. CONCLUSIONS: Cardiac T2* MRI helps to detect cardiac IO in asymptomatic patients. It is important to perform hepatic and cardiac T2* MRI to detect IO in patients with TDT. There was no statistically significant correlation between pathogenic variants of HBB and HFE genes with hepatic and cardiac IO in this cohort of patients.
Assuntos
Proteínas de Transporte de Cátions/genética , Proteína da Hemocromatose , Sobrecarga de Ferro , Receptores da Transferrina , Globinas beta/genética , Talassemia beta , Criança , Feminino , Ferritinas , Proteína da Hemocromatose/genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/genética , Masculino , Mutação , Receptores da Transferrina/genética , Sri Lanka , Talassemia beta/complicações , Talassemia beta/genética , Talassemia beta/terapiaRESUMO
To compare the similarity of the non-patented T2* and the high cost patented R2 (Ferriscan®) MRI techniques in the measurement of liver iron concentration (LIC) in heavily transfused patients with thalassaemia major in a real- life Sri Lankan hospital setup. We compared LIC measured by MRI, obtained 2 weeks apart, using both T2* and R2 techniques in 15 patients with beta thalassaemia major. They all had a history of > 100 units of blood transfusions life long and also a history of sub optimal chelation. MRI R2 and MRI T2* scan values showed a negative correlation (co-rrelation coefficient = - 0.63, p = 0.01) This correlation was strong in lower LICs and progressively decreased with upper LIC values. Thus a significant discrepancy was observed between median values of two MRI technologies (p = 0.0005) with T2* tending to underestimate iron overload especially in those with very high LIC identified by R2. The lack of concordance of T2* and R2 especially in those with very high reading on R2 suggest the potential errors in interpretations that can occur in "non-expert centres"; which are likely to lead to errors in clinical judgement on the intensity of chelation therapy needed.
