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58 Hereditary Hemolytic Anemia in Children
Bugubaeva Makhabat Mitalipovna
Ayan Alam Khan
(1.Associate Professor , HOD Clinical Disciplines , Osh State Medical University , International Medical Faculty .)
(2 .Student, International Medical Faculty, Osh State University, Osh, Kyrgyzstan.)
Abstract
Hereditary hemolytic anemia (HHA) is a group of genetically determined diseases with premature erythrocyte destruction. In children, the diseases cause a significant clinical burden due to anemia, jaundice, growth retardation, and risk of gallstones and splenomegaly. The most common forms are membrane defects (hereditary spherocytosis), enzymopathies (G6PD deficiency, pyruvate kinase deficiency), and hemoglobinopathies (sickle cell disease, thalassemia). Accurate diagnosis relies on a combination of clinical, laboratory, and molecular requirements. Early diagnosis and tailored treatment will prevent morbidity and improve quality of life.
1. Introduction
Inherited hemolytic anemias are hereditary disorders that lead to premature red blood cell (RBC) destruction, resulting in intermittent or chronic anemia. The conditions arise due to defects in either of three key components of the erythrocyte:
• Cell membrane
• Structure of hemoglobin
• Red cell metabolism-associated enzymes
Unlike acquired hemolytic anemias, there are inherited ones present at birth but can become clinically apparent depending on how severe the defect is. Children's presentation can include pallor, jaundice, splenomegaly, and delay in growth and development.
2. Etiopathogenesis
The etiopathogenesis of hereditary hemolytic anemia is classified according to the underlying defect:
2.1 Membranopathies
Protein deficiencies in the erythrocyte membrane lead to abnormal red cell shape and heightened fragility. These are:
• Hereditary spherocytosis (HS): Deficiency of ankyrin, spectrin, or band 3 protein. Spherocytes are sequestered and destroyed in the spleen.
• Hereditary elliptocytosis (HE): Spectrin or protein 4.1 mutations leading to elliptical RBCs.
2.2 Hemoglobinopathies
Abnormal hemoglobin synthesis leads to destruction of RBCs:
• Sickle cell disease (SCD): Mutation in the β-globin gene causing hemoglobin S. Sickling of RBCs is the cause of hemolysis and vaso-occlusion.
• Thalassemias: Overproduction or underproduction of α- or β-globin chains, causing ineffective erythropoiesis and hemolysis.
2.3 Enzymopathies
Red cell enzyme deficiencies impair RBC metabolism and survival:
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Oxidative stress resulting in hemolysis.
• Pyruvate kinase deficiency: Unusual ATP production causes membrane instability and hemolysis.
2.4 Genetic Transmission
• Autosomal dominant in membrane disorders (e.g., HS)
• Autosomal recessive in enzymopathies and severe hemoglobinopathies (e.g., PK deficiency, thalassemia major)
• X-linked in G6PD deficiency
3. Clinical Picture
Clinical presentation depends on the severity and nature of hemolysis:
3.1 Common Features
• Anemia: Pallor, fatigue, growth delay
• Jaundice: Because of unconjugated hyperbilirubinemia
• Splenomegaly: Because of increased sequestration of RBCs
• Gallstones: Chronic hemolysis leads to pigment stones
3.2 Type-specific Presentations
• Hereditary spherocytosis: Intermittent jaundice, mild to moderate anemia, spherocytes on peripheral smear.
• Sickle cell disease: Pain crises, dactylitis, recurrent infections, stroke risk.
• Thalassemias: Severe anemia, frontal bossing, hepatosplenomegaly, skeletal deformities.
• G6PD deficiency: Acute hemolysis caused by drugs, infections, or fava beans.
4. Diagnosis
Diagnosis of hereditary hemolytic anemia requires a combination of laboratory tests and clinical correlation:
4.1 Laboratory Investigations
• Complete Blood Count (CBC): Anemia, reticulocytosis
• Peripheral Blood Smear: Spherocytes (HS), elliptocytes (HE), target cells (thalassemia), sickle cells (SCD)
• Reticulocyte Count: Elevated in hemolytic states
• Bilirubin Levels: Unconjugated hyperbilirubinemia
• Lactate Dehydrogenase (LDH): Elevated in hemolysis
• Haptoglobin: Low in hemolysis
• Direct Antiglobulin Test (Coombs test): Negative in hereditary forms
4.2 Specific Diagnostic Tests
• Osmotic Fragility Test: HS diagnosis
• Hemoglobin Electrophoresis: Thalassemias and SCD
• Enzyme Assays: Pyruvate kinase activity, G6PD activity
• Molecular Genetic Testing: Establishes mutations in difficult cases
5. Differential Diagnosis
Hereditary hemolytic anemia should be distinguished from other causes of hemolysis in the pediatric population:
• Acquired hemolytic anemia: Autoimmune hemolytic anemia (Coombs test positive)
• Infections: Sepsis, malaria
• Nutritional deficiency: Folate or Vitamin B12 deficiency
• Drug- or toxin-induced hemolysis
6. Treatment
Treatment based on severity and type of hemolysis and complications:
6.1 General Measures
• Folic acid supplementation: To support erythropoiesis
• Triggers avoidance: Especially in G6PD deficiency
6.2 Type-specific Interventions
• Hereditary spherocytosis:
- Mild: Supportive
- Severe: Splenectomy (after 5–6 years of age to prevent infection risk)
• Sickle cell disease:
- Hydroxyurea to prevent crises
- Blood transfusions for severe anemia or stroke protection
- Prevention of infection (vaccines, penicillin)
• Thalassemias:
- Regular transfusions of blood
- Iron chelation treatment
- Bone marrow transplantation for selected patients
• G6PD deficiency:
- Avoidance of oxidant drugs and foodstuffs
- Supportive therapy in hemolytic crises
• Pyruvate kinase deficiency:
- Splenectomy for severe disease
- Supportive treatment
6.3 New Therapies
• Gene therapy for β-thalassemia and sickle cell disease
• Pharmacologic chaperones for enzyme deficiency
7. Prognosis
• Differs by type and severity
• Timely detection and adequate treatment significantly improve quality of life
• Regular monitoring for complications such as gallstones, iron overload, and infection
8. Conclusion
Inherited hemolytic anemias in children constitute a heterogeneous group of disorders with common clinical presentations but disparate molecular etiologies. Proper understanding of their etiopathogenesis, clinical presentation, and diagnostic modalities is vital to optimal management. Early diagnosis, prevention, and goal-directed treatment can reduce morbidity and improve outcomes.
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