bims-conane 2025-01-26 papers

Hemoglobin. 2025 Jan 20. 1-5

Characterization and Confirmation of Mildly Unstable Hb Pontoise or α1 63(E12) Ala > Asp and Literature Review.

Bin Tang, Keyi Chen, Lihua Liang, Jie Li, Jicheng Wang, Tianwen He, Hao Guo.

Genotype-phenotype correlation and potential genetic risk in the compound heterozygosity for unstable hemoglobins (UHbs) and α0-thalassemia were discussed. Capillary electrophoresis and gene sequencing helped to establish the diagnosis. Hematological analysis showed the following findings: MCV 80.6 fL, MCH 27 pg, HGB 133 g/L, RBC 4.93 × 1012/L, Hb A: 94%, Hb X: 3.6% (zone 12) and Hb A2: 2.4%. DNA analysis revealed the patient was a Hb Pontoise carrier (HBA1: c.191C > A). Hb Pontoise resulted from an GCC > GAC substitution at codon 63 of the HBA1 genes, but carriers were usually asymptomatic or with only borderline hematological abnormalities. Due to mild instability of Hb Pontoise, its diagnosis relied on genetic diagnosis. Considering the high frequency of thalassemia in South China, accurate genotyping and appropriate genetic counseling should be performed for unstable hemoglobin carriers.

Keywords: Hb Pontoise; Unstable hemoglobin; capillary electrophoresis; rare mutation; the compound heterozygosity for UHbs and α0-thalassemia

DOI: https://doi.org/10.1080/03630269.2025.2451411

Cureus. 2024 Dec;16(12): e76277

Haemoglobin (Hb) AE Bart's Disease in a Young Patient: A Case Report.

Sumaiyah Adzahar, Adibah Daud, Sharifah Nany Rahayu Karmilla Syed Hassan, Mohammad Hudzaifah Nordin, Nabilah Rameli, Nurul Asyikin Nizam Akbar, Razan Hayati Zulkeflee.

Haemoglobin (Hb) AE Bart's disease is a rare form of thalassemia that results from the co-inheritance of Hb E and alpha thalassemia, typically with Hb H disease. The clinical severity can vary depending on the underlying genetic mutations, particularly in the presence of Hb Constant Spring (Hb CS), which is a highly unstable form of alpha thalassemia. Understanding the genetic basis and haematological profiles of Hb AE Bart's disease is crucial for proper diagnosis and management. We report the case of a nine-year-old Malay boy presenting with severe hypochromic microcytic anemia, jaundice, and hepatosplenomegaly. Haemoglobin electrophoresis findings consistent with Hb H Constant Spring disease co-inherited with Hb E. Molecular genetic testing confirmed compound heterozygosity for the South East Asian (SEA) deletion and Hb CS mutation along with heterozygous Hb E. This case highlights the importance of considering complex haemoglobinopathies such as Hb AE Bart's disease in patients presenting with anemia, especially in regions with a high prevalence of thalassemia. Early diagnosis through a combination of Hb electrophoresis and molecular genetic testing is essential for proper management and genetic counseling to prevent long-term complications.

Keywords: hb ae bart’s disease; hb constant spring; hb h disease; sea deletion; thalassemia

DOI: https://doi.org/10.7759/cureus.76277

Int J Hematol. 2025 Jan 21.

The medium-fluorescence reticulocyte ratio is an independent predictor of G6PD deficiency neonates.

Mingliang Rao, Wenna Luo, Baojing Wu.

OBJECTIVE: G6PD deficiency is a potentially life-threatening condition in neonates presenting with hyperbilirubinemia. This study aims to identify clinical and laboratory predictors of G6PD deficiency in neonates presenting with hyperbilirubinemia.
METHODS: This was a retrospective study of 227 term neonates admitted to Heyuan People's Hospital from January 2019 to October 2023. Hematological parameters and bilirubin were compared between those with G6PD deficiency and those with normal G6PD.
RESULTS: Term neonates with G6PD deficiency had higher levels of total bilirubin, indirect bilirubin, mean corpuscular volume, mean corpuscular hemoglobin, immature reticulocyte fraction, high-fluorescence reticulocyte ratio, medium-fluorescence reticulocyte ratio, and content of reticulocytes than those with normal G6PD, but lower levels of red blood cells, hemoglobin, hematocrit, and low-fluorescence reticulocyte ratio. Medium-fluorescence ratios (OR = 1.291, P = 0.028) independently predicted G6PD deficiency in neonates. The optimal cut-off value for medium-fluorescence ratios was > 18.55%. The area under the curve for diagnosing G6PD deficiency was 0.924 (95% confidence interval: 0.886-0.962, P < 0.0001), with a sensitivity of 82.6% and specificity of 86.2%.
CONCLUSION: MFR emerged as a potentially valuable predictor for G6PD deficiency in neonates.

Keywords: Bilirubin; Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency); Hematological parameters; Medium-fluorescence reticulocyte ratio (MFR)

DOI: https://doi.org/10.1007/s12185-025-03916-2

Genet Test Mol Biomarkers. 2025 Jan;29(1): 7-11

Case Report: A Novel Homozygous Variant in the SLX4 Gene Causes Fanconi Anemia.

Sepideh Eisazaei, Majid Naderi, Dor Mohammad Kordi Tamandani.

Background: Fanconi anemia (FA) is a rare genetic disorder that affects multiple systems in the body and is the most prevalent congenital syndrome, leading to bone marrow failure. Twenty-two genes have been identified as contributors to the disease. Significant advancements have been made in the past 2 decades in understanding the genetic and pathophysiological processes involved. Whole exome sequencing (WES) is employed to diagnose rare Mendelian disorders when standard tests fail to provide a definitive pathological diagnosis. However, WES has the potential to reveal pathogenic variants that may complicate the diagnostic process. In this study, the method was chosen to examine SLX4/FANCP. Aims: The goal of our research was to suggest that the new potentially harmful genetic mutation, c.4921dup A>AC (p.Val1641GlyfsTer15), could lead to the development of FA. Methods and Result: This patient was analyzed by performing the WES test, and a homozygous pathogenic variant in the SLX4 gene (c.4921dupA>AC - chr16-3633329-p.Val1641GlyfsTer15) was identified in this patient. The candidate variant was confirmed by Sanger sequencing. The parent of the patient and the fetus of this family were also examined using Sanger sequencing, and they were determined to be carriers and heterozygous. Conclusion: Our research has uncovered a new form of pathogenic genetic variation in the SLX4 gene, providing new insights into the molecular causes of this condition. To date, the c.4921dup A>AC (p.Val1641GlyfsTer15) pathogenic variant has not been observed or reported worldwide. These findings could be valuable for investigating the mechanisms of FA and may offer insights for preventing, diagnosing, and managing the risks associated with this disease.

Keywords: FANCP; Fanconi anemia; SLX4; WES

DOI: https://doi.org/10.1089/gtmb.2024.0467

J Mol Med (Berl). 2025 Jan 21.

Hereditary non-spherocytic hemolytic anemia with GPI mutations successfully treated with allogeneic hematopoietic stem cell transplantation: a first report of two cases.

Huimin Li, Jiali Wang, Liucheng Rong, Jian Li, Yao Xue, Yongjun Fang, Yaping Wang.

Glucose phosphate isomerase (GPI) deficiency caused by GPI gene mutations is a rare heterogenous condition that causes hereditary non-spherocytic hemolytic anemia (HNSHA). Patients who suffer from severe anemia may need more effective treatment. Here, clinical data and genetic testing results of two cases of HNSHA with GPI mutations treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) were retrospectively analyzed. Specifically, two unrelated 6-year-old male patients with severe hemolytic anemia had hemoglobin (Hb) below the normal range despite frequent blood transfusions. Two novel missense mutations in the GPI gene were detected in them, respectively. They underwent peripheral blood stem cell (PBSC) transplantation successfully, and there was no anemia post-transplantation. In conclusion, HNSHA caused by mutations of the GPI gene is inherited in an autosomal recessive (AR) manner. Allo-HSCT offers an acceptable therapeutic efficacy and improvement of quality of life in HNSHA patients with GPI mutations. Our study expands the genetic spectrum of GPI deficiency. KEY MESSAGES: We reported for the first time that two cases of hereditary non-spherocytic hemolytic anemia with GPI mutations successfully treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two novel missense mutations in GPI gene were detected in each of the two cases, respectively, which were predicted to be pathogenic or damaging. Our study expands the genetic spectrum of GPI deficiency. Allo-HSCT offers an acceptable therapeutic efficacy and improvement of quality of life in HNSHA patients with GPI mutations.

Keywords: GPI gene; Allogeneic hematopoietic stem cell transplantation; Hereditary non-spherocytic hemolytic anemia; Missense mutation; Red cell enzymopathies

DOI: https://doi.org/10.1007/s00109-025-02514-3