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27. Hereditary Hemolytic Anemia in Children: Etiopathogenesis, Clinical Picture, Diagnosis, Differential Diagnosis, and Treatment
Bugubaeva Makhabat Mitalipovna
Akash Praful Meshram
(1, Teacher. Pediatrics, International Medical Faculty of Osh State University )
2, Student,(Group 35) International Medical Faculty, Osh State University, Osh, Kyrgyzstan.)
Abstract
Hereditary hemolytic anemias (HHA) are a diverse group of genetic disorders characterized by premature destruction of red blood cells (RBCs). The main categories include membranopathies (e.g., hereditary spherocytosis, elliptocytosis), enzymopathies (e.g., glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency), and hemoglobinopathies (e.g., thalassemia, sickle cell disease). This study aims to analyze the etiopathogenesis, clinical features, diagnostic criteria, and treatment strategies for hereditary hemolytic anemia in children. A comprehensive review of clinical data and literature highlights the importance of early diagnosis and individualized management for improving outcomes and preventing complications such as splenomegaly, gallstones, and growth retardation.
Introduction
Hereditary hemolytic anemias are congenital conditions resulting from intrinsic defects in the red blood cell membrane, enzymes, or hemoglobin structure. These defects lead to increased fragility or abnormal RBC metabolism, causing premature destruction in the spleen or circulation.
Globally, HHA contributes significantly to pediatric morbidity, particularly in regions with high prevalence of hemoglobinopathies such as Africa, Southeast Asia, and the Mediterranean basin. In children, the early presentation of pallor, jaundice, and splenomegaly often leads to misdiagnosis unless supported by hematological investigations. Understanding the underlying molecular mechanisms and developing targeted therapies remain key challenges in pediatric hematology.
Objectives
1. To describe the etiological and genetic mechanisms underlying hereditary hemolytic anemia in children.
2. To identify characteristic clinical manifestations and complications associated with different subtypes.
3. To evaluate diagnostic tools including hematological, biochemical, and molecular techniques.
4. To discuss differential diagnoses distinguishing hereditary hemolytic anemia from acquired hemolytic and other anemic disorders.
5. To review current and emerging treatment strategies, including supportive care, pharmacotherapy, and surgical interventions.
6. To emphasize the importance of early diagnosis and family screening in management and prevention.
Methods
• Study Design: Narrative review and comparative analysis of pediatric hereditary hemolytic anemia cases reported in literature.
• Data Sources: PubMed, Scopus, WHO reports, and pediatric hematology textbooks (2010–2025).
• Inclusion Criteria: Studies involving children (0–18 years) diagnosed with hereditary hemolytic anemia of any genetic type.
• Data Collection: Extracted information on etiology, clinical features, diagnostic markers, and treatment outcomes.
• Analysis: Qualitative synthesis of epidemiological trends, diagnostic accuracy, and therapeutic efficacy.
Study Population and Setting
• Population: Children aged 0–18 years diagnosed with hereditary hemolytic anemia (membranopathies, enzymopathies, or hemoglobinopathies).
• Setting: Pediatric hematology departments, tertiary hospitals, and previously published studies from regions with varying prevalence (Asia, Europe, Africa).
• Sampling Technique: Purposive sampling of clinical studies and case series relevant to the research topic.
Data Sources:
Data were obtained from the following:
• Electronic databases: PubMed, Scopus, Google Scholar, and WHO Global Health Library.
• Journals and textbooks: British Journal of Haematology, Pediatric Blood & Cancer, The Lancet Hematology, and standard pediatric hematology textbooks.
• Search period: January 2010 – September 2025.
• Search terms: “hereditary hemolytic anemia in children,” “RBC membranopathy,” “G6PD deficiency,” “thalassemia,” “sickle cell anemia,” “pediatric hematology,” and “gene therapy in anemia.”
Keywords
Hereditary hemolytic anemia; children; red blood cell disorders; enzymopathies; membranopathies; hemoglobinopathies; spherocytosis; G6PD deficiency; thalassemia; pediatric hematology; splenectomy.
Results
The review identified three major categories of hereditary hemolytic anemia in children:
1. Membranopathies:
• Hereditary spherocytosis (spectrin or ankyrin defects) – presents with anemia, jaundice, and splenomegaly.
• Diagnostic tools: Osmotic fragility test, eosin-5-maleimide (EMA) binding test.
• Treatment: Splenectomy in severe cases.
2. Enzymopathies:
• G6PD deficiency and pyruvate kinase deficiency – lead to episodic hemolysis triggered by oxidative stress or infections.
• Diagnosis: Enzyme activity assays, genetic testing.
• Management: Avoidance of oxidative drugs, folate supplementation, transfusions during crises.
3. Hemoglobinopathies:
• Thalassemia and sickle cell disease – caused by globin gene mutations.
• Manifestations: Chronic anemia, skeletal deformities, hepatosplenomegaly, growth delay.
• Treatment: Regular blood transfusions, iron chelation, hydroxyurea, gene therapy (emerging).
Complications:
• Splenomegaly, gallstones, delayed growth, aplastic crises (especially in parvovirus B19 infection).
• Severe cases require multidisciplinary care involving hematologists and genetic counselors.
Discussion
Hereditary hemolytic anemia represents a heterogeneous group of diseases with overlapping clinical features but distinct genetic bases. Understanding etiopathogenesis allows tailored diagnostic and therapeutic approaches.
• Etiopathogenesis: Defects in RBC membrane proteins (ankyrin, spectrin), enzymes (G6PD, PK), or hemoglobin (β- or α-globin genes) lead to premature hemolysis.
• Clinical Spectrum: Ranges from asymptomatic mild anemia to severe transfusion-dependent states. Neonatal jaundice and splenomegaly are hallmark signs.
• Diagnosis: Requires integration of complete blood count (CBC), reticulocyte count, peripheral smear, biochemical markers (bilirubin, LDH), osmotic fragility test, and genetic testing.
• Differential Diagnosis: Acquired hemolytic anemias (autoimmune hemolysis, infections, toxins), nutritional anemias, and bone marrow failure syndromes.
• Treatment: Supportive measures (folate, transfusion), definitive management (splenectomy, chelation), and curative options (hematopoietic stem cell transplantation, gene therapy).
Advances in molecular diagnostics and gene editing hold promise for personalized treatment and long-term disease control in children.
References
1. Bolton-Maggs PHB, et al. Guidelines for the diagnosis and management of hereditary spherocytosis. Br J Haematol. 2012.
2. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008.
3. Weatherall DJ, Clegg JB. The Thalassemia Syndromes. Blackwell Science, 2010.
4. Gallagher PG. Red cell membrane disorders. Hematology Am Soc Hematol Educ Program. 2013.
5. Beutler E. G6PD deficiency and related enzymopathies. Blood Rev. 2020.
6. Fucharoen S, Winichagoon P. Thalassemia in Southeast Asia: problems and strategy for prevention. Curr Opin Hematol. 2012.
7. Nussenzveig RH et al. Diagnostic approach to hereditary hemolytic anemias in children. Pediatr Blood Cancer. 2021.
8. WHO. Global prevalence of hemoglobin disorders. WHO Technical Report Series. 2020.
9. Mohandas N, Gallagher PG. Red cell membrane: past, present, and future. Blood. 2008.
