Hemoglobin D-Punjab Homozygotes and Double Heterozygotes in Premarital Screening: Case Presentations and Minireview

Hemoglobin D-Punjab Homozygotes and Double Heterozygotes in Premarital Screening: Case Presentations and Minireview



Abstract Views
1372

Downloads
716

Citations

Share

##plugins.themes.bootstrap3.article.sidebar##

##plugins.themes.bootstrap3.article.main##

Hemoglobin D-Punjab is the most common variant of hemoglobin D. In premarital screening, molecular testing is often unavailable, and diagnosis (and marriage guidance) often relies on the hemoglobin analysis, family studies and epidemiological facts. The use of latter methods sometimes results in hemoglobin D-Punjab/β-thalassemia double heterozygote being mistaken for its homozygote, which could be costly. We present the clinical and laboratory characteristics of hemoglobin D-Punjab phenotypes/genotypes in 15 individuals and review similar reports in the literature. We find that the quantity of hemoglobin D-Punjab in homozygotes is higher than in hemoglobin D-Punjab/β-thalassemia double heterozygotes, its fraction > 92% being consistent with homozygosis. The limitations of this diagnostic criterion are discussed, and clinical severity of this and other hemoglobin D-Punjab double heterozygotes reviewed.

Keywords: Hemoglobinopathies; Sickle cell anemia; Thalassemia major; Population genetics; Prevention genetics; Community health services.
  1. Torres LS, Okumura JV, Silva DG, Bonini-Domingos CR (2015) Hemoglobin D Punjab: origin, Distribution and laboratory diagnosis. Rev Bras Hematol Hemoter 37:120–126.
    DOI
     Google Scholar 
  2. Vella F, Lehmann H (1974) Haemoglobin D Punjab (D Los Angeles). J Med Genet 11:341–342.
    DOI
     Google Scholar 
  3. Belhoul KM, Bakir ML, Abdulrahman M (2013) Misdiagnosis of Hb D-Punjab/β-thalassemia is a potential pitfall in hemoglobinopathy screening programs: a case report. Hemoglobin 37:119–123. https://doi.org/10.3109/03630269.2013.769174.
    DOI
     Google Scholar 
  4. Das S, Mashon RS (2015) Coinheritance of Hb D-Punjab and β-thalassemia: diagnosis and implications in prenatal diagnosis. Hemoglobin 39:138–140. https://doi.org/10.3109/03630269.2015.1004335.
    DOI
     Google Scholar 
  5. Stephens AD, Angastiniotis M, Baysal E et al (2012) ICSH recommendations for the measurement of haemoglobin A2. Int J Lab Hematol 34:1–13.
    DOI
     Google Scholar 
  6. Shanthala Devi AM, Rameshkumar K, Sitalakshmi S (2016) Hb D: A not so rare hemoglobinopathy. Indian J Hematol Blood Transfus 32:294–298. https://doi.org/10.1007/s12288-013-0319-3.
    DOI
     Google Scholar 
  7. Heard-Bey F (2001) The tribal society of the UAE and its traditional economy. In: Al Abed I, Hellyer P (eds) United Arab Emirates: A new perspective. Trident Press, London.
     Google Scholar 
  8. Aslan D (2020) Is hemoglobin D trait hematologically silent: comparison with healthy controls and β-thalassemia carriers. J Pediatr Hematol Oncol 42:e698–e701.
    DOI
     Google Scholar 
  9. Zakerinia M, Ayatollahi M, Rastegar M, Amanat SH, Askarinejad AR, Amirghofran S, Haghshenas M (2011) Hemoglobin D (Hb D Punjab/Los Angeles and Hb D Iran) and co-inheritance with alpha- and beta-thalassemia in Southern Iran. Iran Red Crescent Med J 13:493–498.
     Google Scholar 
  10. Mahdavi MR, Jalali H, Kosaryan M, Roshan P, Mahdavi M (2015) β-Globin gene cluster haplotypes of Hb D-Los Angeles in Mazandaran Province, Iran. Genes Genet Syst 90:55–57.
    DOI
     Google Scholar 
  11. El-Kalla S, Baysal E (1998) Alpha-thalassemia in the United Arab Emirates. Acta Haematol 100:49–53.
    DOI
     Google Scholar 
  12. Worthington S, Lehmann H (1985) The first observation of Hb D Punjab beta zero thalassaemia in an English family with 22 cases of unsuspected beta zero thalassaemia minor among its members. J Med Genet 22:377–381.
    DOI
     Google Scholar 
  13. Giordano PC (2013) Strategies for basic laboratory diagnostics of the hemoglobinopathies in multi-ethnic societies: interpretation of results and pitfalls. Int J Lab Hematol 35:465–479.
    DOI
     Google Scholar 
  14. Ozsoylu S (1970) Homozygous hemoglobin D Punjab. Acta Haematol 43:353–359.
    DOI
     Google Scholar 
  15. Silva-Pinto AC, Silva TJ, Moretto EL, Ottoboni MÂ, Rodrigues ES, Covas DT (2014) Blood donor homozygous for Hb D Los Angeles. Transfus Apher Sci 51:219–220.
    DOI
     Google Scholar 
  16. Desai D, Dhanani H, Shah M, Dayal N, Kapoor A, Yeluri S (2003) Homozygous hemoglobin D diseases: A case report. Internet J Path 3:1–4.
     Google Scholar 
  17. Srinivas U, Pati HP, Saxena R (2010) Hemoglobin D-Punjab syndromes in India: a single center experience on cation-exchange high performance liquid chromatography. Hematology 15:178–181.
    DOI
     Google Scholar 
  18. Thornburg CD, Zimmerman SA, Schultz WH, Ware RE (2001) An infant with homozygous hemoglobin D-Iran. J Pediatr Hematol Oncol 23:67–68.
    DOI
     Google Scholar 
  19. Dash S (1987) Blood donor homozygous for haemoglobin D. J Assoc Physicians India 35:874.
     Google Scholar 
  20. Sasi S, 20. Ozturk O, Arikan S, Atalay A, Atalay EO (2018) Time estimations by network of beta globin gene cluster haplotypes linked with Hb D-Los Angeles [β121 (GH4) Glu → Gln GAA → CAA] mutation in the world populations. Mol Genet Genomic Med 6:1181–1187.
    DOI
     Google Scholar 
  21. Hedrick PW (2011) Population genetics of malaria resistance in humans. Heredity 107:283–304.
    DOI
     Google Scholar 
  22. Taghavi Basmanj M, Karimipoor M, Amirian A et al (2011) Co-inheritance of hemoglobin D and β-thalassemia traits in three Iranian families: clinical relevance. Arch Iran Med 14:61–63.
     Google Scholar 
  23. Panyasai S, Rahad S, Pornprasert S (2017) Coinheritance of hemoglobin D-Punjab and β0-thalassemia 3.4 kb deletion in a Thai girl. Asian J Transfus Sci 11:199–202.
    DOI
     Google Scholar 
  24. Adekile AD, Kazanetz EG, Leonova JY, Marouf R, Khmis A, Huisman TH (1996) Co-inheritance of Hb D-Punjab (codon 121; GAA-->CAA) and beta (0) -thalassemia (IVS-II-1;G-->A). J Pediatr Hematol Oncol 18:151–153.
    DOI
     Google Scholar 
  25. Theodoridou S, Alemayechou M, Perperidou P Sinopoulou C, Karafoulidou T, Kiriakopoulou G (2009) Compound heterozygosity for Hb D-Punjab/β-thalassemia and blood donation: Case report. Turk J Hematol 26:100–101.
     Google Scholar 
  26. Fucharoen S, Changtrakun Y, Surapot S, Fucharoen G, Sanchaisuriya K (2002) Molecular characterization of Hb D-Punjab [beta121(GH4)Glu-->Gln] in Thailand. Hemoglobin 26:261–269.
    DOI
     Google Scholar 
  27. Yassin MA, Nair AP, Al Maslamani MS (2020) A case of COVID-19 in a patient with asymptomatic hemoglobin D thalassemia and glucose-6-phosphate dehydrogenase deficiency. Am J Case Rep 21:e925788.
    DOI
     Google Scholar 
  28. Denic S, Agarwal MM, Al Dabbagh B, El Essa A, Takala M, Showqi S, Yassin J (2013) Hemoglobin A2 lowered by iron deficiency and α-thalassemia: should screening recommendation for β-Thalassemia change? ISRN Hematol 2013:858294.
    DOI
     Google Scholar 
  29. Paglietti ME, Satta S, Sollaino MC et al (2016) The problem of borderline hemoglobin a2 levels in the screening for β-thalassemia carriers in Sardinia. Acta Haematol 135:193–199.
    DOI
     Google Scholar 
  30. Denic S, Souid AK, Nagelkerke N, Showqi S, Balhaj G (2011) Erythrocyte reference values in Emirati people with and without α+ thalassemia. BMC Blood Disord 24:11:1.
    DOI
     Google Scholar 
  31. Denic S, Aden B, Nagelkerke N, Essa AA (2013) β-Thalassemia in Abu Dhabi: consanguinity and tribal stratification are major factors explaining the high prevalence of the disease. Hemoglobin 37:351–358.
    DOI
     Google Scholar 
  32. Smith EW, Conley CL (1959) Sickle cell-hemoglobin-D disease. Ann Intern Med 50:94–105.
    DOI
     Google Scholar 
  33. Cawein MJ, Lappat EJ, Brangle RW, Farley CH (1966) Hemoglobin S-D disease. Ann Intern Med 64:62–70.
    DOI
     Google Scholar 
  34. Aflatouni MM, Malek M (1978) Sickle cell hemoglobin D disease 1st reported case in Iran. Acta Med Iran 21:153–160.
     Google Scholar 
  35. Ali Al-Barazanchi ZA, Abdulateef SS, Hassan MK, Jaber RZ (2019) Double heterozygosity for hemoglobin S and D Punjab in Basra, Iraq: A clinical and hematological study of 42 patients. J Appl Hematol 10:134–140.
    DOI
     Google Scholar 
  36. Torres LS, Okumura JV, Belini-Júnior É et al (2016) Phenotypic diversity of sickle cell disease in patients with a double heterozygosity for Hb S and Hb D-Punjab. Hemoglobin 40:356–358
    DOI
     Google Scholar 
  37. Patel DK, Purohit P, Dehury S, et al. (2014) Fetal hemoglobin and alpha thalassemia modulate the phenotypic expression of Hb SD-Punjab. Int J Lab Hematol 36:444–450.
    DOI
     Google Scholar 
  38. Thalagahage KH, Jayaweera JAAS, Kumbukgolla W, Perera N, Thalagahage E, Kariyawasam J, Dissanayake V (2018) HbS/D-Punjab disease: report of 3 cases from Sri Lanka. Indian J Hematol Blood Transfus 34:350–352.
    DOI
     Google Scholar 
  39. Hamidieh AA, Jalili M, Khojasteh O, Ghavamzadeh A (2010) First report of successful stem cell transplantation in a patient with sickle cell hemoglobin D disease. J Pediatr Hematol Oncol 32:397–399.
    DOI
     Google Scholar 
  40. Villanueva H, Kuril S, Krajewski J, Sedrak A (2013) Pulmonary thromboembolism in a child with sickle cell hemoglobin D disease in the setting of acute chest syndrome. Case Rep Pediatr 2013:875683.
    DOI
     Google Scholar 
  41. Tewari S, Brousse V, Piel FB, Menzel S, Rees DC (2015) Environmental determinants of severity in sickle cell disease. Haematologica 100:1108–1116.
    DOI
     Google Scholar 
  42. Gupta SK, Dass J, Saxena R (2015) A rare case of double heterozygous state for HbD and HbE. Indian J Pathol Microbiol 58:126–127.
    DOI
     Google Scholar 
  43. Sharma SK, Gogoi S, Dutta R, Mahanta J (2003) Haemoglobin D in a mongoloid non-tribal family: A report from northeast India. Curr Sci 84:752–753.
     Google Scholar 
  44. Edison ES, Shaji RV, Chandy M, Srivastava A (2011) Interaction of hemoglobin E with other abnormal hemoglobins. Acta Haematol 126:246–248.
    DOI
     Google Scholar 
  45. Hirani S, Gupta S, Veillon D, Patan S, Master S, Mansour R (2020) The curious case of hemoglobin DC disease masquerading as sickle cell anemia. Hematol Rep 12:8519.
    DOI
     Google Scholar 
  46. Sripichai O, Makarasara W, Munkongdee T et al (2008) A scoring system for the classification of beta-thalassemia/Hb E disease severity. Am J Hematol 83:482–484.
    DOI
     Google Scholar 
  47. Chen W, Zhang X, Shang X et al (2010) The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity. BMC Med Genet 11:31.
    DOI
     Google Scholar 
  48. Boreux G, Farquet JJ, Pugin P, Miescher PA, Klein D (1978) Double hétérozygotie hémoglobine C/bêta-thalassémie chez un algérien présentant une suppression totale de la synthèse de l'hémoglobine A [Haemoglobinosis C/beta-thalassemia double heterozygosity in an Algerian patient with total suppression of haemoglobin A synthesis (author’s transl)]. J Genet Hum 26:1–15.
     Google Scholar 
  49. Kumar S, Rana M, Handoo A, Saxena R, Verma IC, Bhargava M, Sood SK (2007) Case report of HbC/beta(0)-thalassemia from India. Int J Lab Hematol 29:381–385.
    DOI
     Google Scholar 
  50. Fattoum S, Guemira F, Abdennebi M, Ben Abdeladhim A (1993) Association HbC/beta-thalassémie. A propos de onze cas observés en Tunisie [HbC/beta-thalassemia association. Eleven cases observed in Tunisia]. Ann Pediatr (Paris) 40:45–48.
     Google Scholar 
  51. Nagel RL, Fabry ME, Steinberg MH (2003) The paradox of hemoglobin SC disease. Blood Rev 17:167–178.
    DOI
     Google Scholar 
  52. Schroeder WA, Powars D, Reynolds RD, Fisher JI (1977) Hb-E in combination with Hb-S and Hb-C in a black family. Hemoglobin 1:287–289.
     Google Scholar 
  53. Pecker LH, Schaefer BA, Luchtman-Jones L (2017) Knowledge insufficient: the management of haemoglobin SC disease. Br J Haematol 176:515–526.
    DOI
     Google Scholar 
  54. Chapman MS, Kiritkumar K, Lund K, Bain BJ (2019) An unusual hemoglobinopathy: compound heterozygosity for hemoglobins C and E. Am J Hematol 94:144.
    DOI
     Google Scholar 
  55. Fucharoen S, Fucharoen G, Sanchaisuriya K, Surapot S (2005) Compound heterozygote states for Hb C/Hb Malay and Hb C/Hb E in pregnancy: a molecular and hematological analysis. Blood Cells Mol Dis 35:196–200.
    DOI
     Google Scholar 
  56. Schroeder WA, Powars D, Reynolds RD, Fisher JI (1977) Hb-E in combination with Hb-S and Hb-C in a black family. Hemoglobin 1:287–289.
    DOI
     Google Scholar 
  57. Masiello D, Heeney MM, Adewoye AH, Eung SH, Luo HY, Steinberg MH, Chui DH (2007) Hemoglobin SE disease: a concise review. Am J Hematol 82:643–649.
    DOI
     Google Scholar 
  58. Knox-Macaulay HH, Ahmed MM, Gravell D, Al-Kindi S, Ganesh A (2007) Sickle cell-haemoglobin E (HbSE) compound heterozygosity: a clinical and haematological study. Int J Lab Hematol 29:292–301.
    DOI
     Google Scholar 

Downloads

Download data is not yet available.
Crossref
Scopus
Google Scholar
Europe PMC

How to Cite

Denic, S., & Souid, A.-K. (2021). Hemoglobin D-Punjab Homozygotes and Double Heterozygotes in Premarital Screening: Case Presentations and Minireview. European Journal of Medical and Health Sciences, 3(1), 90–94. https://doi.org/10.24018/ejmed.2021.3.1.681

Search Panel

 Srdjan Denic
 Google Scholar
 PUBMED
 EJMED Journal
 Abdul-Kader Souid
 Google Scholar
 PUBMED
 EJMED Journal