bims-conane 2025-02-23 papers

Clin Ther. 2025 Feb 18. pii: S0149-2918(25)00009-8. [Epub ahead of print]

Effects of Thalidomide on Metabolism and Lifespan of Red Blood Cell in Patients With β-Thalassemia Major: A Post Hoc Analysis of a Randomized Controlled Trial.

PURPOSE: Recent studies have shown the thalidomide's therapeutic potential in treatment of patients with β-thalassemia major. However, the effect of thalidomide on metabolism and lifespan of red blood cells (RBCs) is rarely reported.
METHODS: This study was a post hoc analysis of a randomized controlled trial (Chinese Clinical Trial Registry, ChiCTR1800015702). One hundred patients with β-thalassemia major were randomly assigned 1:1 to treatment with a placebo or thalidomide. The primary outcomes were the differences in RBC lifespan, reticulocyte count, and peripheral nucleated RBC count of patients after treatment of 12 weeks. Other indicators of hemolytic reaction were also analyzed.
FINDINGS: Compared with the placebo group after treatment of 12 weeks, the thalidomide group showed a longer RBC lifespan (16.29 ± 6.42 vs 12.90 ± 4.98 days; P = 0.004), smaller mean corpuscular volume (68.34 ± 7.79 vs 78.01 ± 6.33 fl; P < 0.001), smaller mean corpuscular hemoglobin (21.62 ± 2.85 vs 24.68 ± 2.69 pg; P < 0.001), and lower lactate dehydrogenase (190.00 [148.00 - 305.00] vs 251.00 [199.20 - 327.80]; P = 0.014). Meanwhile, thalidomide significantly increased the RBC lifespan at 24 weeks (21.24 ± 8.30 days; P < 0.001) and 48 weeks (23.21 ± 8.42 days; P < 0.001) when compared with baseline (12.8 ± 6.0 days).
IMPLICATIONS: Thalidomide increases the RBC lifespan and reduces hemolytic reactions in patients with β-thalassemia major. Chinese Clinical Trial Registry identifier: ChiCTR1800015702.

Keywords: Metabolism; Red blood cells; Thalidomide; β-Thalassemia

DOI: https://doi.org/10.1016/j.clinthera.2025.01.008

Clin Lab. 2025 Feb 01. 71(2):

Pyrimidine-5'-Nucleotidase Deficiency: a New Homozygous NT5C3A Mutation (c.693+1G>A variant).

Damla C Patir, Ajda Gunes, Burak Durmaz, Emin Karaca, Nur Soyer.

BACKGROUND: Erythrocytes have an average lifespan of 120 days, after which they are typically removed by macrophages in the reticuloendothelial system. Hemolytic anemia can shorten erythrocyte lifespan, leading to varying clinical presentations depending on whether hemolysis occurs intravascularly or extravascularly. Among intrinsic causes of hemolysis, pyrimidine 5'-nucleotidase (P5N) deficiency is a notable condition, often presenting as nonspherocytic hemolytic anemia.
METHODS: We report a case of a 65-year-old female patient with systemic lupus erythematosus and a history of splenectomy, who was admitted for evaluation of persistent hemolytic crises. Clinical examination, peripheral blood smear analysis, and genetic testing were performed, including next-generation sequencing to identify mutations in the NT5C3A gene associated with P5N deficiency.
RESULTS: The patient exhibited macrocytic anemia and basophilic stippling on peripheral blood smear, with normal results from osmotic fragility tests and G6PD levels. Genetic testing revealed a homozygous c.693+1G>A variant in the NT5C3A gene, classified as possibly pathogenic based on ACMG criteria. This variant is linked to P5N deficiency, which aligns with the patient's clinical presentation of non-immune hemolytic anemia.
CONCLUSIONS: The identification of the NT5C3A gene mutation through next-generation sequencing highlights the significance of molecular technologies in diagnosing rare forms of hemolytic anemia. This case underscores the necessity for genetic counseling for affected individuals and their families, as well as the importance of continued follow-up and supportive care in managing hemolytic anemia related to enzyme deficiencies.

DOI: https://doi.org/10.7754/Clin.Lab.2024.240807

Front Genet. 2024 ;15 1522204

Identification of a novel SPTB gene splicing mutation in hereditary spherocytosis: a case report and diagnostic insights.

Xiaobing Li, Tingqiang Zhang, Xuemei Li, Li Wang, Qian Li, Qianqian Liu, Chengyin He, Li Zhang, Yongsheng Liu, Junling Tang.

Background: Hereditary spherocytosis (HS) is a group of genetically heterogeneous hereditary hemolytic disorders characterized by anemia, splenomegaly, jaundice, reticulocytosis, and spherical red blood cells on peripheral blood smears. Mutations in key genes, including SPTB, ANK1, SLC4A1, SPTA1, and EPB42, are commonly implicated in HS.
Case Presentation: We report the case of a 22-year-old female presenting with anemia, jaundice, and a family history of splenectomy. Laboratory investigations revealed hemolytic anemia, elevated bilirubin levels, and peripheral blood smear findings consistent with HS. Genetic testing identified a novel SPTB gene splicing mutation (NM_001355436.2: c.1645-1G>A), inherited maternally, which is predicted to disrupt normal RNA splicing and protein synthesis.
Discussion: The identified SPTB mutation expands the known mutation spectrum of the SPTB gene and highlights its role in the pathogenesis of HS. Clinical findings, combined with genetic analysis, confirmed the diagnosis of HS and underscored the importance of comprehensive molecular testing for accurate diagnosis, especially in patients with a strong family history.
Conclusion: This case emphasizes the utility of genetic testing in diagnosing hereditary spherocytosis, particularly for novel gene mutations. Early and accurate molecular diagnosis facilitates better clinical management, family counseling, and treatment decisions for patients with HS.

Keywords: hemolytic anemia; hereditary spherocytosis; jaundice; mutation; novel SPTB gene; splenomegaly

DOI: https://doi.org/10.3389/fgene.2024.1522204

Pediatr Blood Cancer. 2025 Feb 16. e31609

Fava Bean- Versus Non-Fava Bean-Induced Acute Hemolytic Crisis in Children with Glucose-6-Phosphate Dehydrogenase Deficiency: A Prospective Comparative Study.

Gowda Parameshwara Prashanth, Mohammed Al-Shafey, Anita Tandon, Salim Ismail.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a red cell enzymopathy in which exposure to oxidative stressors, such as drugs or fava bean ingestion, can trigger acute hemolytic episodes (AHEs). This study aimed to compare the clinical characteristics of fava bean-induced hemolysis (FBIH) with non-fava bean-induced hemolysis (NFBIH) in children with G6PD deficiency in a high-prevalence setting.
METHODS: A prospective cohort study was conducted at a region referral hospital in Oman. Hospital records of children hospitalized for AHE due to G6PD deficiency over a 3-year period were analyzed. Participants were categorized into FBIH and NFBIH groups based on the documented precipitating factor.
RESULTS: Among the 236 recruited cases, 51.6% AHEs were attributed to FBIH. Children with FIBH were younger, more likely to present with abdominal pain, and had greater severity of hemolysis upon admission (hemoglobin: 4.8 vs. 6.7 g/dL; p < 0.001). Lab markers such as serum ferritin, blood urea, lactate dehydrogenase, and alkaline phosphatase were significantly elevated in FBIH. The least squares regression model demonstrated a strong link between various predictor variables and hemoglobin levels, explaining about 76.6% of the variance in the study cohort.
CONCLUSION: Children with FBIH experience more severe hemolytic episodes compared to those with NFBIH. Our statistical model identified clinical and laboratory parameters potentially useful in early risk stratification during AHEs. Culturally sensitive dietary education of patients and caregivers is necessary, particularly in regions where fava beans are a dietary staple. The potential influence of specific G6PD genotypes within the NFBIH group merits future investigation.

Keywords: G6PD deficiency; Vicia faba; children; fava bean; intravascular hemolysis; prognosis

DOI: https://doi.org/10.1002/pbc.31609

J Infect Dis. 2025 Feb 18. pii: jiaf080. [Epub ahead of print]

G6PD deficiency is associated with an increased risk of acute kidney injury independent of hemolytic complications in children with severe malaria.

Ruth Namazzi, Caroline Kazinga, Giselle Lima-Cooper, Claire Liepmann, Michael J Goings, Olivia Bednarski, Marco Abreu, Tae-Hwi Schwantes-An, Anthony Batte, Robert O Opoka, Chandy C John, Andrea L Conroy.

Acute kidney injury (AKI) is common and predicts mortality in severe malaria. Studies have reported an increased incidence of AKI in males with hemolytic features of SM. G6PD deficiency, an X-linked enzymopathy, can induce hemolysis. We evaluated whether the G6PD African allele (A-) was associated with AKI in children with severe malaria. The prevalence of G6PD deficiency was 16.7% among hemizygous males and 2.4% in females. G6PD deficiency was associated with 2.56-fold odds of AKI (95% CI, 1.33 to 4.93, p=0.005), adjusting for age, sex, site, nutritional status, and features of hemolysis.

Keywords: AKI; G6PD; intravascular hemolysis; sex differences

DOI: https://doi.org/10.1093/infdis/jiaf080