hereditary persistence of fetal hemoglobin-sickle cell disease syndrome

Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome is a rare genetic hemoglobinopathy characterized by high levels of fetal hemoglobin and mild microcytosis with hypochromia. Individuals with this condition generally experience a mild clinical course, although some may present with acute sickle cell manifestations such as pain crises and acute chest syndrome. Prevalence estimates are not well established and the precise genetic basis is still under investigation. The clinical variability often depends on the degree of fetal hemoglobin expression relative to HbS levels.

The clinical features center on abnormal hemoglobin production and red blood cell morphology. A defining finding is the persistent high level of hemoglobin F, which is always present, while HbS hemoglobin is expressed at moderate to high levels in many cases. Affected systems include the hematologic system—with laboratory findings of hypochromic microcytic anemia and reticulocytosis—and the splenic system, which may manifest as splenomegaly, splenic infarction, or even asplenia. In addition, some individuals experience symptoms impacting other systems such as arthralgia, increased red cell sickling tendency, abdominal pain, pulmonary infiltrates, retinopathy, and severe infections. Not all individuals experience all features, and severity varies considerably.

The precise genetic basis of this syndrome is under investigation, and it is thought to result from complex genetic and environmental factors. In this condition, the genotype is characterized by the coexistence of an HbS allele and an HbF allele, with the clinical manifestation largely dependent on the ratio of fetal hemoglobin to sickle hemoglobin. Inheritance details are not well established at this time, which means that understanding of how the condition is passed on remains an area of ongoing research. Genetic counseling may provide further insights for families concerned about inheritance patterns and planning.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the needs of each individual. Because no specific therapies have been approved for this syndrome, a multidisciplinary approach is recommended. Regular surveillance is an essential part of long-term care, helping to identify potential complications early, such as acute chest syndrome or pain crises. Patients should work with their healthcare team and may benefit from consultations with specialists experienced in hemoglobinopathies; genetic counseling is also advised to help families understand the condition and plan for the future.

Outcomes for individuals with hereditary persistence of fetal hemoglobin-sickle cell disease syndrome vary depending on the relative expression of fetal hemoglobin versus HbS. Many individuals with high levels of pancellular fetal hemoglobin remain asymptomatic, while those with heterocellular expression may experience intermittent sickle cell crises and related complications. With current standards of care, many individuals maintain a good quality of life, although the condition may progress differently from one person to another. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition to receive personalized guidance.