bims-conane Biomed News
on Congenital anemias
Issue of 2025–03–09
twelve papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo



  1. J Pediatr Hematol Oncol. 2025 Mar 03.
      Mutations that alter the structure of red blood cells, including the mutations that cause sickle cell disease (SCD), are common globally because they protect against malaria. Patients with SCD rarely develop severe anemia that requires blood transfusions before 6 months of age. We present the case of a patient with SCD who developed severe anemia requiring a blood transfusion at 6 weeks old and subsequent transfusions throughout her first two and a half years of life. Next-generation sequencing genetic testing revealed that the patient also had hereditary pyropoikilocytosis (HPP), a severe form of hereditary elliptocytosis (HE), and was heterozygous for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Following splenectomy, the frequency of her transfusions slightly decreased. This case demonstrates that HPP modifies the severity of SCD and highlights the importance of considering additional hematologic conditions and obtaining genetic testing in patients with SCD and early-onset anemia.
    DOI:  https://doi.org/10.1097/MPH.0000000000003012
  2. Blood Adv. 2025 Feb 28. pii: bloodadvances.2024015574. [Epub ahead of print]
      Genetic depletion of the transcriptional repressor BCL11A in red blood cell precursors alleviates b-hemoglobinopathies by inducing the fetal g-globin genes. However, additional erythroid genes are regulated by BCL11A and the effects of its deficiency on erythropoiesis are insufficiently described. We discovered that Cas9 disruption of the BCL11A intron 2 erythroid enhancer in CD34+ hematopoietic stem and progenitor cells using a clinically approved strategy caused impaired expansion and apoptosis of erythroid precursors in vitro and reduced repopulation of the erythroid compartment after xenotransplantation into immunodeficient mice. Mutant colony-forming unit erythroid cells, proerythroblasts and basophilic erythroblasts exhibited dysregulation of 94 genes (> 2-fold change, FDR < 0.05), 25 of which are likely direct targets of BCL11A. Differentially expressed genes were associated with a range of biological pathways that impact cell expansion and survival. Our findings show that BCL11A regulates additional aspects of erythropoiesis beyond g-globin gene repression, with unknown clinical consequences.
    DOI:  https://doi.org/10.1182/bloodadvances.2024015574
  3. Oman Med J. 2024 Sep;39(5): e680
      Ischemic priapism is a male urologic emergency. Most cases have been linked to genetic conditions such as sickle cell disease and (much more rarely) glucose-6-phosphate dehydrogenase deficiency, and the use of certain drugs. Here, we report the case of a 34-year-old male who was a known case of the recurrent ischemic type of priapism, which was relieved by penile aspiration. Genetic investigation revealed that the patient had glucose-6-phosphate dehydrogenase.
    Keywords:  Glucose-6-Phosphate Dehydrogenase Deficiency; Ischemic; Oman; Priapism
    DOI:  https://doi.org/10.5001/omj.2024.31
  4. Ann Hematol. 2025 Mar 05.
      Sideroblastic anemias (SAs) represent a heterogeneous group of rare hematological disorders characterized by iron accumulation in mitochondria of erythroblasts with ineffective erythropoiesis. SAs are categorized into acquired and congenital forms. Acquired, secondary, and clonal, SA is rare in pediatric populations. Congenital SA (CSA) is classified into syndromic and non-syndromic forms. Herein, we describe three cases of pediatric patients with SA. The diagnosis of SA was based on the presence of type 3 sideroblasts on BM aspirate smear (greater than 15%) and genetic tests. In the first case, the diagnosis of myelodysplastic syndrome with ring sideroblasts (MDS-RS) with somatic SF3B1 mutation was made at the age of 11 years. A whole exome sequencing did not reveal any germinal predisposition for MDS. A wait-and-see strategy was adopted. After one year- of follow-up, no blood transfusion was needed and no further cytopenia occurred. The two other children had presented anemia at an early age and were diagnosed with CSA. The first case was a girl with SCL25A38 gene mutation. For the second one, the diagnosis of aminolevulinic acid synthase 2 deficiency was considered the most plausible given the family history and the favourable response to pyridoxine. Iron overload occurred in both patients with CSA, requiring chelation therapy. In conclusion, Perls' stain remains a valuable tool for guiding the diagnosis of unexplained anemia in pediatric patients. Genetic testing is crucial for the characterization of congenital sideroblastic anemias. The incidence of myeloid neoplasms with ring sideroblasts is exceptional in children, and the long-term prognosis remains undefined.
    Keywords:  ALAS 2 deficiency; Congenital sideroblastic anemia; Myelodysplastic syndrome; Perls’ stain; Ring sideroblasts; SCL25A38 gene mutation; SF3B1 mutation
    DOI:  https://doi.org/10.1007/s00277-025-06266-5
  5. Hemoglobin. 2025 Mar 04. 1-7
      Alpha thalassemia major (ATM) is the most severe form of α-thalassemia, with thousands of cases annually throughout the world. It was historically incompatible with life, with almost all affected individuals dying at or before birth. Recent advances utilizing early, serial intrauterine transfusions have resulted in improved outcomes, including improved neurocognitive functioning and less congenital anomalies. At-risk families should be identified pre-conceptually for counseling and options such as preimplantation genetic testing. ATM, when diagnosed prenatally, requires counseling about termination options and transfusion therapy. Postnatally, aggressive transfusion, in contrast to standard thalassemia transfusion protocols, suppresses ineffective erythropoiesis and hemoglobin Barts formation. These advances have changed the course of ATM in utero and postnatally. Preliminary results suggest iron chelation may be safely administered after one year of age with monitoring, including quantitative liver iron measurements. Patients with ATM can now survive on chronic transfusion therapy and potentially be cured by hematopoietic cell transplantation (HCT). New therapies continue to emerge, including in-utero stem cell transplantation using maternal stem cells and Phase 1 gene therapy trials evaluating reactivation of the embryonic α-globin (zeta) gene and encoding the α-globin gene. Globally, an international working group has been formed to address ATM, which should lead to advances worldwide.
    Keywords:  Diagnosis; alpha thalassemia major; treatment
    DOI:  https://doi.org/10.1080/03630269.2024.2432899
  6. Semin Fetal Neonatal Med. 2025 Feb 25. pii: S1744-165X(25)00007-1. [Epub ahead of print] 101613
      
    Keywords:  Alloimmune; Fetal anemia; Hydrops; Transfusion
    DOI:  https://doi.org/10.1016/j.siny.2025.101613
  7. Hemoglobin. 2025 Mar 04. 1-7
      Thalassemia is a hemoglobinopathy that affects many people worldwide. Although treatments such as iron chelation and safe transfusions have improved life expectancy, patients still experience complications. Thalidomide, with its immunomodulatory and anti-angiogenic properties, has been found to increase the expression of the γ-globin gene and promote erythroid cell proliferation. Our study compared thalidomide-treated and standard therapy groups, assessing health-related quality of life in thalassemia patients using the SF-36 questionnaire tailored for the Indian population. A total of 84 patients (Thalidomide: 50, Standard: 34) were enrolled. Sixty-four percent of patients on thalidomide became transfusion-free within 4-6 months. The mean duration of transfusion requirement in the thalidomide group increased from 20 to 35 days in 30% of patients. Patients aged ≤ 20 years, without splenectomy, and unemployed had significantly better physical health component (PHC) scores with thalidomide therapy compared to standard therapy (P = 0.027, P = 0.0007, and P = 0.045, respectively). On the other hand, patients aged >20 years and with intact spleen had significantly better mental health component (MHC) scores with thalidomide therapy compared to standard therapy (P = 0.006 and P < 0.00001, respectively). Thalidomide therapy showed significantly better MHC scores than standard therapy on all four scales. Thalidomide therapy shows significant promise in improving the HRQoL for thalassemia patients, particularly in those with early initiation, as indicated by enhanced physical and mental health component scores and improved vitality, emotional well-being, role-emotional, and social functioning compared to standard care.
    Keywords:  Quality of life; standard care; thalassemia; thalidomide
    DOI:  https://doi.org/10.1080/03630269.2025.2473526
  8. BMJ Case Rep. 2025 Mar 03. pii: e264795. [Epub ahead of print]18(3):
      Congenital erythropoietic porphyria (CEP) also known as Gunther's disease is a subtype of porphyria. It is an autosomal recessive disorder caused by a mutation in the uroporphyrinogen III gene (URO III) coding for the enzyme UROS synthase, an essential enzyme in the heme synthesis pathway. The condition may present as non-immune hydrops in foetuses, dark-red urine-stained diapers in neonates and skin blistering and mutilation in sun-exposed areas in older children. Enzyme assays and genetic studies are costly and not easily available in low-resource settings; therefore, awareness of the typical phenotype of this rare porphyria is crucial. However, due to the scarcity of reported cases, clinicians remain oblivious to the disease, leading to delays in diagnosis and initiation of treatment, thus contributing to long-term disabilities. We report a case of a male child in early adolescence presenting with classical cutaneous, skeletal and haematological features of CEP.
    Keywords:  Congenital disorders; Genetic screening / counselling; Haematology (incl blood transfusion); Pediatrics; Skin
    DOI:  https://doi.org/10.1136/bcr-2025-264795