Asian Journal of Transfusion Science
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CASE REPORT Table of Contents   
Year : 2020  |  Volume : 14  |  Issue : 2  |  Page : 185-186
Hereditary persistence of fetal hemoglobin

1 Department of Pathology, Blood Bank, Component and Aphaeresis Unit, G. R. Medical College, Gwalior, Madhya Pradesh, India
2 Lal Pathology, SDM Road, Gwalior, Madhya Pradesh, India
3 Department of Pathology, G. R. Medical College, Gwalior, Madhya Pradesh, India

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Date of Submission26-May-2016
Date of Acceptance06-Dec-2017
Date of Web Publication19-Dec-2020


Hereditary persistence of fetal hemoglobin (HPFH) is a benign condition in which significant fetal hemoglobin production continues well into adulthood, disregarding the normal shutoff point after which only adult-type hemoglobin should be produced. The percentage of incorrect expression might be as low as 10%–15% or as high as 100% of the total hemoglobin, usually higher in homozygotes than in heterozygotes. The present case is a typical example of homozygous HPFH.

Keywords: Hereditary persistence of fetal hemoglobin, heterozygotes, homozygotes

How to cite this article:
Sharma DC, Singhal S, Woike P, Rai S, Yadav M, Gaur R. Hereditary persistence of fetal hemoglobin. Asian J Transfus Sci 2020;14:185-6

How to cite this URL:
Sharma DC, Singhal S, Woike P, Rai S, Yadav M, Gaur R. Hereditary persistence of fetal hemoglobin. Asian J Transfus Sci [serial online] 2020 [cited 2023 Mar 30];14:185-6. Available from:

   Introduction Top

Hereditary persistence of fetal hemoglobin (HPFH) is a condition with significant fetal hemoglobin (HbF) production which continues in adulthood. This is usually caused by mutations in the β- or α-globin gene cluster or the γ promoter gene region. As first discovered in Nigeria by Edington and Lehmann,[1],[2] HPFH has been encountered in people of African descent in Uganda,[3] Jamaica[4],[5] and in the United States,[6],[7],[8],[9],[10],[11],[12] and in a single Caucasian family in Greece.[13] The anomaly has been encountered in the homozygous and heterozygous state. Heterozygotes (up to 30% HbF) have displayed no other abnormality of hemoglobin synthesis (A-F) or have been heterozygous in addition for hemoglobin S (S-F), hemoglobin C (C-F), or thalassemia (Thai-F). Homozygote: only one person apparently homozygous for the anomaly has been discovered,[11] a child of 33 months. In persons with sickle cell disease, high levels of HbF as found in a newborn, or as found abnormally in persons with HPFH, the HbF causes the sickle cell disease to be less severe. In essence, the HbF inhibits polymerization of HbS. A similar mechanism occurs with persons who have sickle cell trait. Approximately 40% of the hemoglobin is in the HbS form while the rest is in normal HbA form. The HbA form interferes with HbS polymerization.[14] Delta beta thalassemia and HPFH constitute a heterogeneous group of disorders characterized by absent or reduced synthesis of adult hemoglobin (Hb A) and increased synthesis of HbF. Coinheritance of these disorders with other beta chain hemoglobinopathies, such as beta thalassemia and the sickle cell (beta s) gene, can result in attenuation of the clinical severity of these hemoglobinopathies owing to the increased Hb F levels. The molecular basis of these disorders is quite heterogeneous and consists of both deletion and nondeletion types of mutations. The characterization of these molecular defects has provided new insights on the structure and function of important regulatory elements that are involved in the normal control of expression of the beta- and gamma-globin genes and in hemoglobin switching.

   Case Report Top

A 50-year-old male, father of a β-thalassemia major patient, reported having HbF, i.e., 94.90% without any symptoms while being investigated for the thalassemic patient's family status.

Family history

Wife is a known case of thalassemia minor with the history of three miscarriages. Family has an 8-month live baby with thalassemia major. No other live member (maternal/paternal) was available for the further investigation.


Father's hemoglobin by high performance liquid chromatography (HPLC)/electrophoresis is HbF - 94.90%, Hb A - 2.60%, HbA2-2.0%, and others - 0.50%. Hb concentration - 15.10 g% with erythrocytosis (RBC count - 6.37 million/mm3). Child – hemoglobin HPLC/electrophoresis – HbF - 91.60%, Hb A - 6.0%, HbA2-2.1%, and others - 0.30%. Mother – reported as β-thalassemia minor.

   Discussion Top

By 6 months of age, a shift from gamma globin to beta globin (HBB) gene expression occurs, reducing the amount of (HbF; α2 γ2) produced so that the major form of hemoglobin present is Hb A (α2 β2). Although residual amounts of Hb F are produced throughout life, the majority of healthy adults have <1% Hb F. HPFH results from mutations within the beta globin gene cluster that alter normal hemoglobin switching. Heterozygotes for HPFH-associated deletions typically have high levels of Hb F (up to 30%) with normal red blood cell indices while homozygous or compound heterozygous, when two deletions associated with HPFH are identified, individuals typically have Hb F levels approaching 100% with mild erythrocytosis. The present case is provisionally diagnosed as homozygous HPFH because HbF is >30% and other hemoglobins, i.e. Hb-S (S-F), hemoglobin C (C-F), and Thalassemia (Thai-F) were absent, that are present in heterozygous HPFH. Cases of heterozygous HPFH were reported from various regions of India[15],[16],[17] and from overseas in African and Greek descendents.[3],[4],[5] The prevalence of heterozygous HPFH in African inhabitants is 0.1%.[18] To the best of our knowledge, few cases of homozygous HPFH have been reported till date.[11],[19],[20] Hence, the present case is among the rare cases of homozygous HPFH and should be built-in records.

   Conclusion Top

HPFH is an anomaly of hemoglobin production apparently caused by mutant gene that inhibits synthesis of hemoglobin A and A2. The above case is a classical example of homozygous HPFH in a 50-year-old healthy asymptomatic male.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Edington GM, Lehmann H. Expression of the sickle-cell gene in Africa. Br Med J 1955;1:1308-11.  Back to cited text no. 1
Expression of the sicklecell gene in Africa. Br NI J 1955;2:1328.  Back to cited text no. 2
Jacob GF, Rapzer AB. Hereditary persistence of foetal haemoglobin production, and its interaction with the sickle-cell trait. Br J Haematol 1958;4:138-49.  Back to cited text no. 3
Went LN, Maciver JE. An unusual type of hemoglobinopathy resembling sickle cell-thalassemia disease in a Jamaican family. Blood 1958;13:559-68.  Back to cited text no. 4
Maciver JE, Went LN. Hereditary persistence of foetal haemoglobin: A family study suggesting allelism of the F gene to the S and C haemoglobin genes. Br J Haematol 1961;7:373-81.  Back to cited text no. 5
Herman EC Jr., Conley CL. Hereditary persistence of fetal hemoglobin. A family study. Am J Med 1960;29:9-17.  Back to cited text no. 6
Bradley TB Jr., Conley CL. Studies of an inherited disorder manifested by persistence of fetal hemoglobin. Trans A Am Physicians 1960;73:72.  Back to cited text no. 7
Olivia J, Myerson RM. Hereditary persistence of fetal hemoglobin. Am J Med Sci 1961;241:215-7.  Back to cited text no. 8
Bradley TB Jr., Brawner JN, Conley CL. Further observations on an inherited anomaly characterized by persistence of fetal hemoglobin. Bull Johns Hopkins Hosp 1961;108:242.  Back to cited text no. 9
Kraus AP, Koch B, Burckett L. Two families showing interaction of haemoglobin C or thalassaemia with high foetal haemoglobin in adults. Br Med J 1961;1:1434-6.  Back to cited text no. 10
Wheeler JT, Krevans JR. The homozygous state of persistent fetal hemoglobin and the interaction of persistent fetal hemoglobin with thalassemia. Bull Johns Hopkins Hosp 1961;109:217-33.  Back to cited text no. 11
Thompson RB, Mitchener JW, Huisman TH. Studies on the fetal hemoglobin in the persistent high Hb-F anomaly. Blood 1961;18:267-84.  Back to cited text no. 12
Fessas P. Hereditary persistence of foetal haemoglobin and its combination with alpha- and with beta-thai- assaemia. In: Haemoglobin-Collo-quium, Lehinann H, Betke K, eds. Stuttgart: Ceorg Thieme Verlag; 1962. p. 82.  Back to cited text no. 13
Vinay K, Abul KA, Nelson F, Jon A. Robbins and Cotran Pathologic Basis of Disease, Professional Edition: Expert Consult – Online (Robbins Pathology) (Kindle Locations 33411-33412). Kindle Edition. Gurgaon, India: Elsevier Health; 2009.  Back to cited text no. 14
Ghosh K, Hasan SW, Kumar S. Hereditary persistence of foetal haemoglobin in Northwest India. Trop Geogr Med 1988;40:209-12.  Back to cited text no. 15
Balgir RS. Hereditary persistence of foetal haemoglobin in a tribal family of Orissa, India. Natl Med J India 2004;17:138-40.  Back to cited text no. 16
Nadkarni A, Wadia M, Gorakshakar A, Kiyama R, Colah RB, Mohanty D, et al. Molecular characterization of delta beta-thalassemia and hereditary persistence of fetal hemoglobin in the Indian population. Hemoglobin 2008;32:425-33.  Back to cited text no. 17
Becker GA, Rossi EC. The interaction of hereditary persistence of fetal hemoglobin and beta thalassemia. Ann Intern Med 1966;65:1071-5.  Back to cited text no. 18
Ringelhann B, Acquaye CTA, Oldham JH, Konotey-Ahulu FID, Yawson G, Sukumaran P.K, et al. Homozygotes for the Hereditary Persistence of Fetal Hemoglobin: The ratio of Gγ to Aγ chains and biosynthetic studies. Biochemical Genetics 1977;15:1083–96.  Back to cited text no. 19
Siegel W, Cox R, Schroeder W, Huisman TH, Penner O, Rowley PT, et al. An adult homozygous for persistent fetal hemoglobin. Ann Intern Med 1970;72:533-6.  Back to cited text no. 20

Correspondence Address:
Dr. Dharmesh Chandra Sharma
2-B, J. A. Hospital Campus, Gwalior - 474 009, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajts.AJTS_71_16

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