Management of Hereditary Persistence of Fetal Hemoglobin (HPFH)
Adults with hereditary persistence of fetal hemoglobin require no treatment, as this is a benign, asymptomatic condition that does not cause clinical disease. 1
Clinical Characteristics and Natural History
HPFH is a rare genetic disorder where fetal hemoglobin (HbF) persists into adulthood instead of being replaced by adult hemoglobin A1 by 6-12 months of age. 1 The condition is characterized by:
- HbF levels of 10-20% in heterozygotes (compared to <1% in normal adults) 2, 3
- Complete absence of hematological abnormalities despite elevated HbF 4
- No clinical symptoms or complications in affected individuals 1
- Incidental discovery during screening for other hemoglobinopathies 1
Diagnostic Confirmation
When HPFH is suspected, confirm the diagnosis through:
- Hemoglobin electrophoresis showing elevated HbF levels (typically 10-20% in heterozygotes) 2, 3
- Molecular genetic testing to identify specific mutations (point mutations in gamma-globin gene promoters or deletions) 2, 5
- Exclusion of other causes of elevated HbF including hemoglobinopathies, leukemias, and bone marrow failure syndromes 1
A critical pitfall is misdiagnosing HPFH as sickle cell disease or other hemoglobinopathies, as occurred in the reported case literature. 1 The key distinguishing feature is that HPFH patients are completely asymptomatic with normal hematological parameters aside from elevated HbF. 1, 4
Management Approach
No therapeutic intervention is required for HPFH itself. 1, 4 The management consists of:
- Reassurance that this is a benign condition requiring no treatment 1
- Accurate diagnosis to prevent unnecessary interventions for misdiagnosed conditions 1
- Genetic counseling for family planning, particularly important because compound heterozygosity with beta-thalassemia can cause thalassemia intermedia 5
- Family screening to identify other affected individuals and provide appropriate counseling 5
Clinical Significance and Genetic Counseling
While HPFH itself requires no treatment, genetic counseling is essential because:
- Compound heterozygosity with beta-thalassemia produces thalassemia intermedia phenotype (more severe than HPFH alone) 5
- Homozygotes for HPFH show only mild microcytic anemia 5
- HPFH acts as a severity modulator in other hemoglobinopathies, making knowledge of carrier status clinically relevant 4
The frequency of HPFH is approximately 1 in 1,000 individuals in studied populations, making awareness of this condition important for proper diagnosis. 4
Key Clinical Pearls
- HPFH is a "blessing in disguise" as the persistent HbF can ameliorate the severity of co-inherited hemoglobinopathies 1
- No follow-up monitoring is required for isolated HPFH beyond initial diagnostic confirmation 1, 4
- Distinguish HPFH from pathological causes of elevated HbF by the absence of anemia, hemolysis, or other hematological abnormalities 1