Hereditary Hemolytic Anemias

(Hemoglobinopathies, Membranopathies, Enzymopathies)

Hereditary hemolytic anemias are genetic disorders caused by structural and functional defects of red blood cells (erythrocytes). These disorders are based on abnormalities in hemoglobin structure, membrane stability, or enzymatic activity. All of them may lead to premature erythrocyte destruction (hemolysis), resulting in chronic anemia, jaundice, and splenomegaly.

1. Hemoglobinopathies

Hemoglobinopathies are hereditary disorders that affect the quantity or structure of hemoglobin, the protein that carries oxygen.

Main types include beta- and alpha-thalassemias, sickle cell anemia, and other rare hemoglobinopathies such as HbE, HbC, and HbD.

Manifestations: anemia, growth retardation, painful crises (in sickle cell anemia), splenomegaly, hepatomegaly, gallstones, and bone deformities.

Diagnosis: hemoglobin electrophoresis, HPLC, genetic testing.

2. Membranopathies

This group of disorders is caused by mutations in erythrocyte membrane proteins, leading to abnormal cell shape and stability.

Main types include spherocytosis (spherical erythrocytes), elliptocytosis (elliptical erythrocytes), and pyropoikilocytosis (multiple deformities).

Manifestations: jaundice, splenomegaly, gallstones, hemolytic crises.

Diagnosis: peripheral blood smear, osmotic fragility test, EMA binding test.

3. Enzymopathies

Enzymopathies result from hereditary deficiencies or defects of erythrocyte enzymes, rendering cells vulnerable to oxidative or mechanical stress.

Main types include glucose-6-phosphate dehydrogenase (G6PD) deficiency (the most common enzymatic disorder worldwide), pyruvate kinase deficiency (leading to impaired energy metabolism and hemolysis), and other rare enzymatic defects (e.g., glutathione reductase, hexokinase deficiency).

Manifestations: anemia, jaundice, stress-induced hemolysis (triggered by drugs, infections, or dietary factors).

Diagnosis: enzyme activity assays, family history.