Coinheritance of Hb D-Punjab andβ-Thalassemia: Diagnosis and Implications in Prenatal Diagnosis

Abstract

Hb D-Punjab (HBB: c.364G>C) is an abnormal hemoglobin (Hb) associated with genetic risk in association with Hb S (HBB: c.20A>T). In addition, misdiagnosing homozygosis for hemizygosis may have implication for genetic risk assessment. We present the diagnostic utility of high performance liquid chromatography (HPLC) in differential diagnosis between the Hb D-Punjab homozygote and the Hb D-Punjab/β-thalassemia (β-thal) genotype. The Hb A2 level measurement may not be a reliable parameter to differentiate between the two conditions. In a screening program for risk prediction, the genotype should be confirmed by family study and/or molecular analysis. Misdiagnosis can have potentially adverse implications in a prenatal diagnosis (PND) program, particularly in areas where consanguinity is common and this Hb D-Punjab variant occurs.

Analysis of the population genetic structure of Hb D‐Los Angeles [β121 (GH4) Glu→Gln GAA→CAA] in Denizli, Turkey; genetic diversity, historical demography and estimation of the mutation rates based on haplotype variation

“…Hb D‐Los Angeles is an asymptomatic abnormal type of hemoglobin with no clinical importance. Conversely, the presence of this Hb is an important parameter for premarital screening, leading to prenatal misdiagnosis (Bahadır, ; Belhoul, ; Das and Mashon, ). In the Denizli province, the most common abnormal hemoglobin variant is Hb D‐Los Angeles [β121(GH4) Glu→Gln] with a frequency of 57% of the total abnormal hemoglobins observed (Atalay, ).…”

Coinheritance of hemoglobin D-Punjab and β0-thalassemia 3.4 kb deletion in a Thai girl

“…Consistency with the previous study showed that cases with coinherited HbD-Punjab and β 0 -thalassemia had only mild to moderate anemia. [ 2 ] In this study, the HbA 2 level measured by HPLC was 3.2% which was in the reference ranges (<3.5%). On HPLC chromatogram, the normal (3.3%) and elevated (6.4%) HbA 2 levels had been reported in two siblings who coinherited HbD-Punjab with the same β 0 -thalassemia mutation (codon 30, AGG>ACG).…”

“…[ 1 ] HbD-Punjab is quite prevalent in Pakistan, Northwest India, China, Middle East countries, and also in many other parts of the world with the overall frequency of 0.2%–3.0%. [ 2 3 4 ] Both the heterozygote and homozygote for HbD-Punjab are clinically silent conditions. However, the coinheritance of HbD-Punjab with HbS [β6(A3) Glu→Val; HBB: C.20A>T] results in mild clinical symptoms to severe conditions with sickle cell disease.…”

“…However, the prevalence of compound heterozygosity for HbD-Punjab and β-thalassemia reported at the Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran from 2006 to 2011 was 0.6%,[ 6 ] and a few cases of compound heterozygosity for HbD-Punjab and β 0 -thalassemia were reported in India, Saudi Arabia, and England. [ 2 4 7 ] These cases had mild to severe anemia with hepatosplenomegaly, Hb values between 80 and 120 g/L, and typical thalassemic indices and morphological change of red cells. HbF values are slightly elevated (1%–7%) while HbA 2 values are varied from 2.9% to 6.4%.…”

“…HbF values are slightly elevated (1%–7%) while HbA 2 values are varied from 2.9% to 6.4%. [ 2 7 ] The normal value of HbA 2 in a sample with coinheritance of HbD-Punjab and β 0 -thalassemia could result in the misdiagnosis of β-thalassemia carrier and inappropriate genetic counseling, as in the case reported by Belhoul et al . [ 8 ] In this study, we reported for the first time of the coinheritance of HbD-Punjab with β 0 -thalassemia in a Thai girl.…”