Hereditary persistence of fetal hemoglobin

Hereditary Persistence of Fetal Hemoglobin (HPFH) is a rare genetic condition in which an individual continues to produce the fetal form of hemoglobin, known as fetal hemoglobin (HbF), into adulthood. Unlike the more common adult hemoglobin (HbA), HbF has a higher affinity for oxygen, which can be beneficial under certain physiological conditions. HPFH is characterized by the continued production of HbF at levels significantly higher than what is typically observed after infancy, where it usually decreases to less than 1% of total hemoglobin.

Etiology and Genetics

HPFH can be inherited in an autosomal dominant or recessive pattern, depending on the specific genetic mutation involved. The condition is caused by mutations in the genes that encode the gamma-globin chain of hemoglobin, specifically the HBB gene cluster on chromosome 11. These mutations lead to a failure in the switching process from gamma-globin (fetal) to beta-globin (adult) production, resulting in the continued synthesis of HbF.

Clinical Presentation

Individuals with HPFH are typically asymptomatic and the condition is often discovered incidentally during routine blood tests that reveal an elevated level of HbF. In some cases, HPFH may be identified during investigations for mild anemia or when a family member is diagnosed with a hemoglobinopathy, such as sickle cell disease or beta-thalassemia.

Diagnosis

The diagnosis of HPFH is based on the demonstration of increased HbF levels in the absence of other conditions that can elevate HbF, such as anemia, leukemia, or pregnancy. Hemoglobin electrophoresis, high-performance liquid chromatography (HPLC), or DNA analysis can be used to quantify HbF levels and identify specific genetic mutations.

Management

As HPFH is generally asymptomatic and does not lead to health complications, specific treatment is not required. However, knowledge of the condition is important for the interpretation of hemoglobin studies and for genetic counseling, especially in families with a history of hemoglobinopathies.

Genetic Counseling

Genetic counseling is recommended for individuals with HPFH and their families to discuss the inheritance pattern, implications for family members, and the association with other hemoglobin disorders. Prenatal testing may be offered to couples with a family history of HPFH who wish to know the status of their fetus.

Association with Hemoglobinopathies

The presence of HPFH can ameliorate the clinical severity of coexisting hemoglobinopathies, such as sickle cell disease and beta-thalassemia, due to the beneficial effects of HbF on oxygen delivery and its interference with the polymerization of sickle hemoglobin or the imbalance of globin chains.

Conclusion

Hereditary Persistence of Fetal Hemoglobin is a genetic condition with significant implications for individuals and families affected by hemoglobinopathies. While it is generally benign, understanding the genetic and clinical aspects of HPFH is crucial for accurate diagnosis, management, and genetic counseling.