Thalassemia Reports

12 pages, 308 KiB

Open AccessFeature PaperReview

Is the Role of Hepcidin and Erythroferrone in the Pathogenesis of Beta Thalassemia the Key to Developing Novel Treatment Strategies?

by Tsz Yuen Au, Shamiram Benjamin and Oskar Wojciech Wiśniewski

Thalass. Rep. 2022, 12(3), 123-134; https://doi.org/10.3390/thalassrep12030017 - 09 Sep 2022

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Abstract

Thalassemia is a disease of erythrocytes that varies largely on its genetic composition and associated clinical presentation. Though some patients may remain asymptomatic, those with a complicated course may experience severe anemia early in childhood, carrying into adulthood and requiring recurrent blood transfusions [...] Read more.

Thalassemia is a disease of erythrocytes that varies largely on its genetic composition and associated clinical presentation. Though some patients may remain asymptomatic, those with a complicated course may experience severe anemia early in childhood, carrying into adulthood and requiring recurrent blood transfusions as a pillar of symptom management. Due to the consequences of ineffective erythropoiesis and frequent transfusions, patients with severe beta thalassemia may be subsequently susceptible to hemochromatosis. In light of the established role of hepcidin and erythroferrone in the pathogenesis of beta thalassemia, this review aims to discuss current clinical trials and studies in the field while presenting clinical implications of the HAMP gene polymorphisms and novel treatments. Research suggested incorporating erythroferrone and serum hepcidin testing as a part of routine workups for beta thalassemia, as they could be a predictive tool for early iron accumulation. Furthermore, ameliorating low hepcidin and high erythroferrone appeared to be crucial in treating beta thalassemia and its complications due to iron overload. Currently, hepcidin-like compounds, such as minihepcidins, LJPC-401, PTG-300, VIT-2763, and agents that promote hepcidin production by inhibiting TMPRSS6 expression or erythroferrone, were shown to be effective in restoring iron homeostasis in preliminary studies. Moreover, the natural bioactives astragalus polysaccharide and icariin have been recently recognized as hepcidin expression inductors. Full article

18 pages, 3123 KiB

Open AccessArticle

Going Back to Fundamentals: Three Marriageable Actions for Thalassemia and Carrier Population Management

by Sehjeong Kim, Hamda AlDhaheri and So-Yeun Kim

Thalass. Rep. 2022, 12(3), 105-122; https://doi.org/10.3390/thalassrep12030016 - 06 Sep 2022

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Abstract

We investigated the impact of three marriageable actions: normal-to-carrier, carrier-to-normal, and carrier-to-carrier marriages on thalassemia and carrier populations. The well-known strategy is limiting the carrier-to-carrier marriage to reduce the thalassemia population. Thus, the other two marriageable actions were often ignored. Other than a [...] Read more.

We investigated the impact of three marriageable actions: normal-to-carrier, carrier-to-normal, and carrier-to-carrier marriages on thalassemia and carrier populations. The well-known strategy is limiting the carrier-to-carrier marriage to reduce the thalassemia population. Thus, the other two marriageable actions were often ignored. Other than a simple explanation of their genetic consequences, their important aspect in the thalassemia inheritance mechanism has never been studied at the population level. Moreover, there is no mathematical model investigating problem of interest for blood disorders at the population level. Hence, we developed a mathematical model to examine the possibility of eradication/reduction of thalassemia and carrier populations through each of the three marriageable actions in the long-term. We conducted computer simulations with the demographic data of the United Arab Emirates in which high thalassemia carrier prevalence is identified. We found that promoting more carrier-to-normal marriage will eventually have the same effects on marriage reconsideration for carrier-carrier couples, contributing to the reduction of the carrier population in the long-term. Interestingly, the normal-to-carrier marriage does not necessarily have a similar effect on thalassemia and carrier populations as that of the carrier-to-normal marriage. Thus, the two marriageable actions should be distinguished and also seriously considered in education and public awareness campaigns for thalassemia. Full article

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4 pages, 415 KiB

Open AccessCase Report

Co-Inheritance of Heterozygous β⁰-Thalassemia with Single Functional α-Globin Gene: Challenges of Carrier Detection in Pre-Marital Screening Program for Thalassemia

by Hossein Jalali, Hossein Karami, Mohammad Reza Mahdavi and Mehrad Mahdavi

Thalass. Rep. 2022, 12(3), 101-104; https://doi.org/10.3390/thalassrep12030015 - 29 Aug 2022

Cited by 1 | Viewed by 1486

Abstract

This is a report of a couple with abnormal hematological indices who were investigated for α & β-thalassemia mutations. Based on CBC and capillary hemoglobin electrophoresis results, the male and female subjects were β & α-thalassemia carriers, respectively. Multiplex-Gap-PCR and Sanger sequencing techniques [...] Read more.

This is a report of a couple with abnormal hematological indices who were investigated for α & β-thalassemia mutations. Based on CBC and capillary hemoglobin electrophoresis results, the male and female subjects were β & α-thalassemia carriers, respectively. Multiplex-Gap-PCR and Sanger sequencing techniques were used for the identification of mutations on α and β-globin genes. The DNA test showed the presence of c.315 + 1 G > A mutation on β-globin gene of male subject while the female case had – ^MED double gene deletion and c.427T > C mutation on α-globin and, interestingly, she was also a carrier for c.315 + 1 G > A mutation on β-globin gene. Cases with the coinheritance of heterozygous β⁰-thalassemia with one functional α-globin gene have normal HbA2 levels that may lead to their being misdiagnosed as β-thalassemia carriers, especially in premarital screening programs for thalassemia. Therefore, β-globin gene sequencing is recommended in cases with normal Hb electrophoresis and reduced hematological indices in premarital screening programs for thalassemia, especially in regions with a high frequency of β-globin mutations, in order to identify all the β-thalassemia carriers. Full article

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11 pages, 1337 KiB

Open AccessArticle

Relationships among Physical Activity, Pain, and Bone Health in Youth and Adults with Thalassemia: An Observational Study

by Ellen B. Fung, Elijah K. Goldberg, Sakina Bambot, Raquel Manzo and Ashutosh Lal

Thalass. Rep. 2022, 12(3), 90-100; https://doi.org/10.3390/thalassrep12030014 - 11 Aug 2022

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Abstract

Patients with thalassemia (Thal) engage in less physical activity than non-Thal populations, which may contribute to pain and osteoporosis. The purpose of this study was to assess relationships between physical activity, pain, and low bone mass in a contemporary sample of patients with [...] Read more.

Patients with thalassemia (Thal) engage in less physical activity than non-Thal populations, which may contribute to pain and osteoporosis. The purpose of this study was to assess relationships between physical activity, pain, and low bone mass in a contemporary sample of patients with Thal. Seventy-one patients with Thal (50 adults ≥18 years, 61% male, 82% transfusion-dependent) completed the Brief Pain Inventory Short Form and validated physical activity questionnaires for youth and adults. Nearly half of the patients reported daily somatic pain. Using multiple regression, after controlling for age and gender, sedentary behavior was positively associated with pain severity (p = 0.017, r² = 0.28). Only 37% of adult participants met CDC recommendations for physical activity. Spine BMD Z-score was higher (−2.1 ± 0.7) in those who met activity guidelines compared to those who did not (−2.8 ± 1.2, p = 0.048). A positive relationship was observed between self-reported physical activity (hours/week) and hip BMD Z-score in adults with Thal after controlling for transfusion status and sedentary activity time (p = 0.009, r² = 0.25). These results suggest that decreased physical activity and increased sedentary behavior contribute to low bone mass, which may be related to pain severity in some patients with Thal. Studies focused on increasing physical activity may contribute to improved bone health and reduced pain in patients with Thal. Full article

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5 pages, 2460 KiB

Open AccessCase Report

A Patient with Sickle Cell Disease and Recurrent Venous Thromboembolism after Renal Transplantation

by Rosario Di Maggio, Alessandra Giuliano, Disma Renda, Giuseppina Calvaruso, Simona Raso, Lorella Pitrolo, Antonio Carroccio and Aurelio Maggio

Thalass. Rep. 2022, 12(3), 85-89; https://doi.org/10.3390/thalassrep12030013 - 20 Jul 2022

Cited by 1 | Viewed by 1579

Abstract

Venous thromboembolism (VTE) is a life-threatening complication, especially in case of recurrence. The appropriate duration of anticoagulant treatment following the first event is crucial. Risk factors that increase the risk of recurrence of VTE are many, and include medications, kidney disease, renal transplantation [...] Read more.

Venous thromboembolism (VTE) is a life-threatening complication, especially in case of recurrence. The appropriate duration of anticoagulant treatment following the first event is crucial. Risk factors that increase the risk of recurrence of VTE are many, and include medications, kidney disease, renal transplantation (RT), and a diagnosis of sickle cell disease (SCD). There are currently no guidelines that define the duration of anticoagulant therapy after the first event in a patient with RT. We report a case of recurring episodes of VTE after RT in a SCD patient. Our case suggests that the use of a long-term anticoagulant treatment may be recommended in patients with SCD and RT after the first event of VTE. Full article

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12 pages, 613 KiB

Open AccessSystematic Review

Molecular Heterogeneity of Hb H Disease in India

by Pallavi Thaker, Namrata Mahajan, Malay B. Mukherjee and Roshan B. Colah

Thalass. Rep. 2022, 12(3), 73-84; https://doi.org/10.3390/thalassrep12030012 - 06 Jul 2022

Viewed by 2342

Abstract

Alpha thalassemia is an autosomal recessive disorder caused by large deletions and/or point mutations in the α- globin genes. Hemoglobin H (Hb H) disease is most frequently due to deletion of three of the four α globin genes associated with variable clinical severity [...] Read more.

Alpha thalassemia is an autosomal recessive disorder caused by large deletions and/or point mutations in the α- globin genes. Hemoglobin H (Hb H) disease is most frequently due to deletion of three of the four α globin genes associated with variable clinical severity depending on the genotype. There are few reports on Hb H disease in Indians where genotyping has been done and we have reviewed the molecular and clinical heterogeneity of these cases. An electronic search for relevant articles was conducted using two journal databases, i.e., PubMed and Science Direct using the key words “Hb H Disease”, “Hemoglobin H”, “α-thalassemia”, “mutations”, “molecular heterogeneity”, “case reports” and “India”. This review was performed based on preferred reporting items for the systematic review and meta-analysis protocols (PRISMA-P) guidelines. The molecular spectrum of Hb H disease in Indians includes the most common [-α^3.7, -α^4.2, --^SA, Poly A (AATAAA→AATA--), Hb Sallanches], rare [--^SEA, --^MED, IVS 1nt 1 (G→A), Hb Koya Dora, Hb Sun Prairie], very rare [Hb Iberia, Hb Seal Rock, Hb Zürich-Albisrieden] and novel [Codon 76 (+T) and --^Kol] α-globin gene mutations inherited largely as compound heterozygotes with considerable clinical variability. The molecular diagnosis of Hb H disease is important for genetic counseling and management. Full article

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18 pages, 3137 KiB

Open AccessArticle

Direct Chromosomal Phasing: An Easy and Fast Approach for Broadening Prenatal Diagnostic Applicability

by Stefania Byrou, George Christopoulos, Agathoklis Christofides, Christiana Makariou, Christiana Ioannou, Marina Kleanthous and Thessalia Papasavva

Thalass. Rep. 2022, 12(3), 55-72; https://doi.org/10.3390/thalassrep12030011 - 01 Jul 2022

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Abstract

The assignment of alleles to haplotypes in prenatal diagnostic assays has traditionally depended on family study analyses. However, this prevents the wide application of prenatal diagnosis based on haplotype analysis, especially in countries with dispersed populations. Here, we present an easy and fast [...] Read more.

The assignment of alleles to haplotypes in prenatal diagnostic assays has traditionally depended on family study analyses. However, this prevents the wide application of prenatal diagnosis based on haplotype analysis, especially in countries with dispersed populations. Here, we present an easy and fast approach using Droplet Digital PCR for the direct determination of haplotype blocks, overcoming the necessity for acquiring other family members’ genetic samples. We demonstrate this approach on nine families that were referred to our center for a prenatal diagnosis of β-thalassaemia using four highly polymorphic single nucleotide variations and the most common pathogenic β-thalassaemia variation in our population. Our approach resulted in the successful direct chromosomal phasing and haplotyping for all nine of the families analyzed, demonstrating a complete agreement with the haplotypes that are ascertained based on family trios. The clinical utility of this approach is envisaged to open the application of prenatal diagnosis for β-thalassaemia to all cases, while simultaneously providing a model for extending the prenatal diagnostic application of other monogenic diseases as well. Full article

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4 pages, 587 KiB

Open AccessCase Report

Hb Mazandaran (α1) α51 Gly > Cys(CE9), c.154 GGC > TGC: A Novel Haemoglobin Variant of α1-Globin Gene

by Hossein Jalali, Mohammad Reza Mahdavi, Mahan Mahdavi and Adeleh Abbasi

Thalass. Rep. 2022, 12(3), 51-54; https://doi.org/10.3390/thalassrep12030010 - 22 Jun 2022

Cited by 1 | Viewed by 1470

Abstract

This is a report of a novel variant of the α1-globin gene—(α1) α51 Gly > Cys (CE9), c.154 GGC > TGC, named Hb Mazandaran, which was observed in an Iranian family. This variant gives rise to a previously undescribed haemoglobin variant that was [...] Read more.

This is a report of a novel variant of the α1-globin gene—(α1) α51 Gly > Cys (CE9), c.154 GGC > TGC, named Hb Mazandaran, which was observed in an Iranian family. This variant gives rise to a previously undescribed haemoglobin variant that was undetectable by capillary haemoglobin electrophoresis (CE). This variant was detected in two cases in combination with β-globin mutation, and it does not seem to be associated with severe haematological abnormalities in the carriers. Full article

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Thalass. Rep., Volume 12, Issue 3 (September 2022) – 8 articles

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