Lepore disease is a rare, inherited blood disorder affecting the body’s ability to produce normal hemoglobin. Hemoglobin, a protein in red blood cells, carries oxygen from the lungs to tissues. This condition is a type of hemoglobinopathy, a genetic disorder that alters hemoglobin structure or production. Individuals with Lepore disease produce an altered form of hemoglobin.
The Genetic Origin of Lepore Disease
Lepore disease originates from a genetic error during cell division, forming a unique hybrid gene. This error is an unequal crossing-over event between the delta-globin and beta-globin genes on chromosome 11. Normally, these genes produce distinct globin chains that form adult hemoglobin. In Lepore disease, a segment of the delta-globin gene fuses with a segment of the beta-globin gene.
This fusion creates a single, abnormal gene. The protein from this gene is an altered globin chain, different from normal delta and beta chains. This abnormal globin chain combines with alpha-globin chains to form unstable Hemoglobin Lepore (Hb Lepore). The body produces Hb Lepore at a reduced rate, and it is less stable than normal hemoglobin.
Clinical Manifestations and Symptoms
The severity of Lepore disease symptoms depends on whether an individual inherits one or two copies of the fusion gene. With one copy (Lepore trait or heterozygous state), individuals are usually asymptomatic. Some may have mild microcytic anemia, characterized by smaller red blood cells, which typically does not require medical intervention.
Inheriting two copies (homozygous state or Lepore disease) leads to severe symptoms, usually emerging in early childhood. These often resemble beta-thalassemia major. Individuals suffer from severe, chronic anemia, causing profound fatigue, weakness, and pallor due to insufficient oxygen. The body compensates by producing more red blood cells, leading to an enlarged spleen (splenomegaly).
Chronic anemia and compensatory bone marrow expansion can lead to complications. These include bone deformities, especially in the facial bones and skull, as the bone marrow works overtime. Growth retardation and delayed puberty are also common in severely affected children.
Diagnosis Process
Diagnosing Lepore disease typically begins with routine blood tests that can indicate an underlying issue with red blood cell production. A complete blood count (CBC) is often the initial step, which may reveal microcytic anemia, where red blood cells are smaller and paler than usual. This finding suggests a problem with hemoglobin synthesis, prompting further investigation.
A crucial step in confirming Lepore disease involves specialized hemoglobin analysis techniques. Methods such as hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) are employed to separate and identify different types of hemoglobin present in the blood. These tests can specifically detect the presence of the abnormal Hemoglobin Lepore. The characteristic pattern of Hb Lepore, often appearing in conjunction with reduced levels of normal adult hemoglobin, provides strong diagnostic evidence.
For a definitive diagnosis, particularly to differentiate it from other hemoglobinopathies, genetic testing is performed. This advanced testing directly analyzes an individual’s DNA to confirm the presence of the delta-beta fusion gene. Genetic testing offers the most precise confirmation of Lepore disease, allowing for accurate counseling and family planning.
Treatment and Management Strategies
Treatment for Lepore disease primarily focuses on managing symptoms, especially in individuals with the severe homozygous form. Regular blood transfusions are central to managing severe chronic anemia. These transfusions provide healthy red blood cells, improving oxygen delivery to tissues and alleviating fatigue and weakness. Transfusion frequency depends on individual severity and response, often occurring every few weeks.
Repeated blood transfusions, while life-saving, lead to iron overload, an accumulation of excess iron in the body. This excess iron can damage organs like the heart, liver, and endocrine glands. To prevent this, iron chelation therapy involves medications that bind to and remove excess iron. These agents can be given orally or through subcutaneous infusions.
Other supportive measures include daily folic acid supplements, which help the bone marrow produce new red blood cells. In some cases, surgical removal of the spleen (splenectomy) may be considered if an enlarged spleen significantly contributes to anemia or discomfort. For severely affected individuals, hematopoietic stem cell transplantation, also known as a bone marrow transplant, is a potential curative option. This procedure replaces faulty blood-forming cells with healthy cells from a compatible donor.
References
Hemoglobin Lepore. National Organization for Rare Disorders (NORD). Accessed July 23, 2025.
Huisman, T. H. J., & Schroeder, W. A. (1986). Hemoglobinopathies and Thalassemias: Clinical, Biochemical, and Genetic Aspects. Churchill Livingstone.
Rund, D., & Rachmilewitz, E. A. (2005). Beta-thalassemia. New England Journal of Medicine, 353(11), 1135-1146.