Prenatal diagnostic errors in hemoglobin Bart’s hydrops fetalis caused by rare genetic interactions of α-thalassemia

Kritsada Singha; Supawadee Yamsri; Kanokwan Sanchaisuriya; Goonnapa Fucharoen; Supan Fucharoen

doi:10.1515/dx-2024-0114

Article

Prenatal diagnostic errors in hemoglobin Bart’s hydrops fetalis caused by rare genetic interactions of α-thalassemia

Kritsada Singha , Supawadee Yamsri , Kanokwan Sanchaisuriya , Goonnapa Fucharoen and Supan Fucharoen

Published/Copyright: September 18, 2024

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From the journal Diagnosis Volume 12 Issue 2

Abstract

Objectives

To describe rare genetic interactions of α-thalassemia alleles causing Hb H disease and Hb Bart’s hydrops fetalis which could lead to diagnostic errors in a routine practice.

Methods

Hematological and molecular characterization were carried out in a Thai family with a risk of having fetus with Hb Bart’s hydrops fetalis.

Results

Both parents were found to be the thalassemia intermedia patients associated with unusual forms of Hb H disease. DNA analysis of common α-thalassemia mutations in Thailand identified α⁺-thalassemia (-α^{3.7 kb del}) and unknown α⁰-thalassemia in the father and α⁰-thalassemia (--^SEA) with unknown α⁺-thalassemia in the mother. Fetal DNA analysis unlikely identified a homozygosity for α⁰-thalassemia (--^SEA/--^SEA). Further analysis identified that the father carried a rare South African α⁰-thalassemia in combination with α⁺-thalassemia (--^SA/-α), whereas the mother was a patient with Hb H-Queens Park disease (--^SEA/αα^QP). The fetus was, in fact, a compound heterozygote for (--^SA/--^SEA).

Conclusions

As shown in this study, routine screening for α-thalassemia at prenatal diagnosis in the region should include both common and rare α⁰-thalassemia alleles found in the population to effectively prevent a fatal condition of Hb Bart’s hydrops fetalis syndrome.

Keywords: hemoglobin H disease; α0-thalassemia; α+-thalassemia; Hb Bart’s hydrops fetalis

Corresponding author: Dr. Supan Fucharoen, Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand, E-mail: supan@kku.ac.th

Funding source: Mahasarakham University

Award Identifier / Grant number: none

Funding source: Khon Kaen University

Award Identifier / Grant number: RP67-2-Research Center KKU-001

Research ethics: The study was conducted in accordance with the principle of the Helsinki Declaration. The study protocol received ethical approval from the Institutional Review Board (IRB) of Khon Kaen University, Thailand (HE652154).
Informed consent: Informed consent was obtained from all individuals included in this study.
Author contributions: Kritsada Singha designed the study, performed experiments, analyzed the data, and developed the initial manuscript. Supawadee Yamsri helped in the routine genetic analysis of the cases. Kanokwan Sanchaisuriya and Goonnapa Fucharoen analyzed the data and interpretation of the cases. Supan Fucharoen supervised results interpretation, designed and facilitated the study, acquired a research grant, and critically revised and approved the final manuscript. All authors approved the final submitted version. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: Not applicable.
Competing interests: The authors state no conflict of interest.
Research funding: This study was financially supported by Khon Kaen University, Thailand, to SF (Contract ID: RP67-2-Research Center KKU-001), and Faculty of Medicine, Mahasarakham University, Thailand, to KrS.
Data availability: Further inquiries or data in this study can be directed to the corresponding author.

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Received: 2024-07-02

Accepted: 2024-08-27

Published Online: 2024-09-18

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Articles in the same Issue

https://doi.org/10.1515/dx-2024-0114

Keywords for this article

hemoglobin H disease; α0-thalassemia; α+-thalassemia; Hb Bart’s hydrops fetalis