Where is fetal hemoglobin produced

Three types of hemoglobin are synthesized in humans depending on the stage of development. Embryonic hemoglobin is produced before birth, fetal hemoglobin HbF during foetal life, and adult hemoglobin after birth. Foetal hemoglobin production is switched off soon after birth although the time of switch over is not know.

Hemoglobin is structurally made up of 2 alpha and 2 non-alpha chains; in addition, HbF has 2 - gamma chains and the predominant adult blood HbA1 has 2 beta chains. A replacement of glutamic acid of the beta chain by valine at the 6 th position gives rise to a sickle cell disorder. This change, called hemoglobin S HbS , is an abnormal hemoglobin 1.

On exposure to low oxygen concentration, the HbS precipitates into elongated crystals appearing as sickled, instead of a biconcave disc. Sickle cell disease is characterized by occlusion events in the vascular that results in pain, organ failure and, occasional, death 2 , 3 , 4 , 5. Studies have revealed that HbF usually disappears from red blood of infants after about 6 months 6.

However the exact time of disappearance of HbF may vary and the signal that determines the switch from fetal to adult hemoglobin is not known. HbF may be found in certain conditions such as childhood anaemia, myeliod leukeamia, hereditary persistence and sickle cell crisis 7 , 8. It is not clear how HbF concentration will affect the severity of crisis in sickle cell individuals and in sickle cell variants.

The objective of this study is to determine the waning time of HbF during infancy and HbF persistence in later life.

In addition to determine the sickle cell variants of patients attending a sickle cell clinic and to investigate the possible function of HbF among various members of a family with sickle cell variants. The cross sectional study was purely laboratory based with partial clinical observation.

Children on admission, either routinely after birth or for simple illness such as diarrhoea and malaria were recruited. Those with transfusion and or complicated diseases were excluded.

Venous blood was collected from infants, aged 0—12 months, on admission at a military and children's hospitals in Accra. About 2 ml blood was drained into EDTA sequestering tube and washed 3 times with saline solution. The blood in tube was centrifuge and frozen for 1 hour to thaw and hemolyse. Carbon tetracycline CCl 4 was added to separate cell membrane from the stroma. Blood collected from adults at the clinic was also hemolysed and stored for later use. The membrane was placed in an electrophoresis tank containing Tris buffer and volts applied for 40 mins.

The strip was removed with a forceps, hot oven dried and analyzed. Colorimetric method with alkaline was used to estimate HbF levels because HbF is more resistant to denaturation. About 0. At a sickle cell clinic at Korle bu hospital in Accra, patients who reported with sickle cell crisis and related ailments were recruited and tested for their sickle cell types using the electrophoresis method described above.

Those recruited had clinical manifestation of sickle cell disease. A sickle cell positive patient with HbF had her family members recruited and further examined for their sickle cell status. They were recruited because the family members were available since they resided on the University of Ghana campus. Both laboratory based electrophoresis and clinical observations were done on the family members.

A structured questionnaire was administered to the family members to determine the form and frequency of crisis they experience.

Out of the infants recruited, 10 were dropped due to difficulties in obtaining enough blood. A total of 90 infants were examined for their fetal hemoglobin, HbF, levels.

Ten each were aged 1, 2, 3, 4, 5 and 6 months and five each aged 7, 8, 9, 10, 11 and 12 months. HbF levels was highest at birth reaching It decreased steadily to a mean of However, high levels of HbF were found in 11 infants aged 6 months and above.

Six infants aged 6 months, had HbF that ranged from 0. None of these HbF was detected by paper electrophoresis.

All other recruits aged 6 to 12 months were negative for HbF. At the Korle-bu sickle cell clinic in Accra, adults, aged 1 to 80 years, were examined for their sickle cell types. All those examined had sickle cell crisis and one patient of SS type who had measurable HbF levels had her family members further examined for their sickle cell status.

In another study, 68 sickle cell positive adults by microscopy were examined for HbF presence. A family of six adults, including 2 parents, were examined for their sickle cell types and the presence of HbF. The father and the mother were aged 45 and 34 years and the offspring 20, 17, 14 and 8 years.

Fetal hemoglobin, HbF was present in the blood of the father and the daughter. The mother and the only son with AS had no detectable HbF. The mother and the son, both with AS types, experienced severe crisis. The pedigree of the family is shown in Fig 2. This confirms earlier studies that the waning period of HbF is between 5 and 6 months 6. The waning off of HbF in infants is due to the switching off from fetal to adult hemoglobin.

Since the time and the mechanism of the HbF switch off is not known, it was not possible to compare and correlate HbF disappearance by the two methods.

Probably these children with elevated HbF may be suffering from one of these diseases, although the particular one was not investigated. The study confirmed earlier findings that HbF is higher in sickle cell adults sufferers than in non-sickle cell subjects. It also presents primary observation on the relations between HbF levels and severity of crisis in sickle cell types within a family.

The other members with AS types had crisis and were found to have no observable HbF. This suggests that HbF increases in sicklers and most likely to protect them from crisis. We do not know whether the mother and son were both only AS since AS individuals rarely experience severe painful crisis. It may be possible that the nylon membrane electrophoresis method used was too insensitive to separate out other abnormal hemoglobins or else 40 minutes was too short for better separation.

Futher studies are needed on this family with more sensitive electrophoresis method and full clinical observation done. Konotey et al. In that study, the mean HbF level for SS patients was 7. These values were far higher than those obtained in sickle cell patients in Nigeria.

We do not know whether environmental factors affect the level of HbF. Further studies are necessary to establish the relation between HbF levels and severity of crisis in different sickle cell types and in different settings.

Till this date correction of hemoglobin disorders such as sickle cell disease is not available at the DNA level. Conventional treatment is aimed at reducing the patient's complains and preventing chronic or irreparable organ damage. Transmission therapy has a place in major hemoglobin disorders including sickle cell diseases. In sickle cell hemoglobin therapy, the goal is to dilute the HbS containing erythrocytes to ensure better tissue oxygenation and thus prevent vascular occlusion.

Increasing the patient's amount of fetal hemoglobin is the most promising target. Previous studies involving administering the drug hydroxyurea HU to Black American sickle cell patients, increased HbF significantly and revealed a significant decrease of the frequency of yearly crisis Research towards the understanding the mechanism of the transition from fetal to adult hemoglobin synthesis and possible reversion to fetal haemoglobin is important. This study demonstrated that fetal hemoglobin HbF waned off at 6 months after birth, but HbF persist in some adults.

This book is distributed under the terms of the Creative Commons Attribution 4. Turn recording back on. National Center for Biotechnology Information , U. StatPearls [Internet]. Search term. Physiology, Fetal Hemoglobin Daniel P.

Author Information Authors Daniel P. Introduction Fetal hemoglobin HbF is the dominant form of hemoglobin present in the fetus during gestation. Cellular Fetal hemoglobin has a vital role in the transport of oxygen from maternal to fetal circulation. Development The evolution of hemoglobin follows gene mutations, such as gene duplication, gene conversion, and translocation of genes in ancient hemoproteins.

Related Testing Fetal hemoglobin is useful in evaluating various conditions in pregnancy and the neonate. Pathophysiology Fetal hemoglobin is of great significance in the pathophysiology of hemoglobinopathies.

Clinical Significance One medical application of the properties of HbF is in the management of sickle cell anemia. Review Questions Access free multiple choice questions on this topic. Comment on this article. References 1. Fossen Johnson S. Methemoglobinemia: Infants at risk. Cochrane Database Syst Rev. Eur J Clin Nutr. Insight into the complex pathophysiology of sickle cell anaemia and possible treatment.

Eur J Haematol. Trends Genet. Erythropoiesis: insights into pathophysiology and treatments in Mol Med. Hardison RC. Evolution of hemoglobin and its genes. Cold Spring Harb Perspect Med. Application of the 'Apt test' in prenatal diagnosis to evaluate the fetal origin of blood obtained by cordocentesis: results of 30 pregnancies.

Prenat Diagn. Accuracy of the haemoglobin alkaline denaturation test for detecting maternal blood contamination of fetal blood samples for prenatal karyotyping.

Arch Pathol Lab Med. Mol Diagn Ther. Genetic therapies for sickle cell disease. Semin Hematol. Int J Hematol. Pediatr Clin North Am. National Institutes of Health Consensus Development Conference statement: hydroxyurea treatment for sickle cell disease. Ann Intern Med. Physiology, Fetal Hemoglobin. In: StatPearls [Internet].

In this Page. Related information. Similar articles in PubMed. N-terminal contributions of the gamma-subunit of fetal hemoglobin to its tetramer strength: remote effects at subunit contacts. Protein Sci. Human globin knock-in mice complete fetal-to-adult hemoglobin switching in postnatal development. Mol Cell Biol. Epub Dec Fetal hemoglobin HbF synthesis in baboons, Papio cynocephalus. Analysis of fetal and adult hemoglobin synthesis during fetal development. Front Cell Dev Biol.

Epub Apr 1.