Hemoglobin Barts
Hemoglobin Barts, abbreviated Hb Barts, is an abnormal type of hemoglobin that consists of four gamma globins. It is moderately insoluble, and therefore accumulates in the red blood cells. Hb Barts has an extremely high affinity for oxygen, so it cannot release oxygen to the tissue. Therefore, this makes it an inefficient oxygen carrier. As an embryo develops, it begins to produce alpha-globins at weeks 5–6 of development. When both of the HBA1 and HBA2 genes which code for alpha globins becomes dysfunctional, the affected fetuses will have difficulty in synthesizing a functional hemoglobin. As a result, gamma chains will accumulate and form four gamma globins. These gamma globins bind to form hemoglobin Barts.[1] It is produced in the disease alpha-thalassemia and in the most severe of cases, it is the only form of hemoglobin in circulation. In this situation, a fetus will develop hydrops fetalis and normally die before or shortly after birth, unless intrauterine blood transfusion is performed.[2]
Since hemoglobin Barts is elevated in alpha thalassemia, it can be measured, providing a useful screening test for this disease in some populations.[3]
The ability to measure hemoglobin Barts makes it useful in newborn screening tests. If hemoglobin Barts is detected on a newborn screen, the patient is usually referred for further evaluation since detection of hemoglobin Barts can indicate either one alpha globin gene deletion, making the baby a silent alpha thalassemia carrier, two alpha globin gene deletions (alpha thalassemia), or hemoglobin H disease (three alpha globin gene deletions). Deletion of four alpha globin genes was previously felt to be incompatible with life, but there are currently 69 patients who have survived past infancy.[4][5]
| Genotypes | Alpha-Globin Gene Deletions | Clinical Component |
| αα/αα | 0 | Normal |
| -α/αα | 1 | Silent Carrier |
| --/αα or -α/-α | 2 | Alpha-Thalassemia Trait |
| --/-α | 3 | Hb H Disease |
| --/-- | 4 | Fetal Hydrops |
Table 1: α represents the presence of α-globin gene and- represents the deletion of α-globin gene.[6]
The chance of a fetus developing Hemoglobin Bart's hydrops fetalis is dependent upon if one or both parent carries the alpha-thalassemia trait. Due to this disease being incompatible with life, diagnosis for it is done prenatally.[7] Early detection of Hemoglobin (Hb) Bart's disease before the development of hydrops fetalis is crucial because fetuses that develop hydrops fetalis will either be stillborn or may die shortly after birth. There can be early pregnancy termination to prevent serious complications for the baby or mother. Studies shows that in 11 to 14 weeks of gestation, sonographic markers can associate affected from unaffected pregnancies. It was found that the most sensitive marker was CT ratio and MCA‐PSV.[8]
Parents at risk of having a child with Fetal Hydrops can continue their pregnancy with regular ultrasounds and intrauterine blood transfusion. Babies of such parents are born with no edema or major neurological defects, and eventually, this disease can be cured with Haematopoietic Stem Cell Transplantation. A newly developed diagnostic test, called Immunochromatography (IC) Strip Tests, uses monoclonal antibodies to detect Hemoglobin Barts in red blood cells' lysate. This diagnostic test is validated for positive and negative predictive values. It is also cheap and easy, making regular screening for alpha-thalassemia a plausible possibility.[9][10]
Anemia is a factor in fetuses with Hemoglobin Bart's disease as there is an "increased cardiac output" and hypovolemia as the tissues of the fetus require oxygen because of the gamma globulin's high affinity for oxygen. This deprives the tissues of receiving oxygen to function well. The symptoms of anemia occur within the first trimester.[11]
This variant of hemoglobin is so called as it was discovered at St Bartholomew's Hospital in London, often abbreviated to Barts.[12]
Notes
[edit]- ^ Al-Allawi NA, Shamdeen MY, Rasheed NS (2010). "Homozygosity for the Mediterranean a-thalassemic deletion (hemoglobin Barts hydrops fetalis)". Annals of Saudi Medicine. 30 (2): 153–155. doi:10.4103/0256-4947.60523. PMC 2855068. PMID 20220267.
- ^ "Pathophysiology of alpha thalassemia". www.uptodate.com. Retrieved 2016-08-30.
- ^ van der Dijs FP, Volmer M, van Gijssel-Wiersma DG, Smit JW, van Veen R, Muskiet FA (September 1999). "Predictive value of cord blood hematological indices and hemoglobin Barts for the detection of heterozygous alpha-thalassemia-2 in an African-Caribbean population". Clinical Chemistry. 45 (9): 1495–1500. doi:10.1093/clinchem/45.9.1495. PMID 10471652.
- ^ Songdej D, Babbs C, Higgs DR (March 2017). "An international registry of survivors with Hb Bart's hydrops fetalis syndrome". Blood. 129 (10): 1251–1259. doi:10.1182/blood-2016-08-697110. PMC 5345731. PMID 28057638.
- ^ Songdej, Duantida; Babbs, Christian; Higgs, Douglas R. (March 9, 2017). "An international registry of survivors with Hb Bart's hydrops fetalis syndrome". ashpublications.org.
- ^ Fogel BN, Nguyen HL, Smink G, Sekhar DL (April 2018). "Variability in State-Based Recommendations for Management of Alpha Thalassemia Trait and Silent Carrier Detected on the Newborn Screen". The Journal of Pediatrics. 195: 283–287. doi:10.1016/j.jpeds.2017.11.048. PMID 29273175. S2CID 4349631.
- ^ Wu MY, Xie XM, Li J, Li DZ (October 2015). "Neonatal screening for α-thalassemia by cord hemoglobin Barts: how effective is it?". International Journal of Laboratory Hematology. 37 (5): 649–653. doi:10.1111/ijlh.12376. PMID 25955662. S2CID 40335193.
- ^ Sirichotiyakul S, Luewan S, Srisupundit K, Tongprasert F, Tongsong T (March 2014). "Prenatal ultrasound evaluation of fetal Hb Bart's disease among pregnancies at risk at 11 to 14 weeks of gestation". Prenatal Diagnosis. 34 (3): 230–234. doi:10.1002/pd.4293. PMID 24318930. S2CID 37146677.
- ^ Hui PW, Pang P, Tang MH (February 2022). "20 years review of antenatal diagnosis of haemoglobin Bart's disease and treatment with intrauterine transfusion". Prenatal Diagnosis. 42 (9): 1155–1161. doi:10.1002/pd.6125. PMID 35226373. S2CID 247157134.
- ^ Pata S, Laopajon W, Pongpaiboon M, Thongkum W, Polpong N, Munkongdee T, et al. (2019-10-29). "Impact of the detection of ζ-globin chains and hemoglobin Bart's using immunochromatographic strip tests for α0-thalassemia (--SEA) differential diagnosis". PLOS ONE. 14 (10): e0223996. Bibcode:2019PLoSO..1423996P. doi:10.1371/journal.pone.0223996. PMC 6818768. PMID 31661492.
- ^ Luewan S, Tongprasert F, Srisupundit K, Tongsong T (April 2015). "Fetal cardiac Doppler indices in fetuses with hemoglobin Bart's disease at 12-14weeks of gestation". International Journal of Cardiology. 184: 614–616. doi:10.1016/j.ijcard.2015.02.053. PMID 25770840.
- ^ Ager JA, Lehmann H (April 1958). "Observations on some fast haemoglobins: K, J, N, and Bart's". British Medical Journal. 1 (5076): 929–931. doi:10.1136/bmj.1.5076.929. PMC 2028335. PMID 13523233.