A 8 years old male from Punjab, a north-Indian state presented with history of fever since one week. Past history revealed two prior hospitalizations for fever and anemia. History of multiple blood transfusions was present. Family history was noncontributory. On examination, pallor was noted along with splenomegaly (5 cms below costal margin).
His hemogram revealed moderate anemia of 82 g/L with normocytic normochromic indices (Mean Corpuscular Volume: 91.9fl and Mean Corpuscular Hemoglobin: 29.2 pg) and increased Red Cell Distribution Width of 18.1%. Reticulocyte count was increased (7.3%). Peripheral blood film examination showed many sickled cells (Figure 1). High pressure liquid chromatography (HPLC, Bio-Rad Variant II) revealed characteristic criss-crossed twin peaks in S and D window of 33.8% and 43.6% respectively along with an HbF of 12.6%, and HbA2 of 3.5% (Figure 2). Cellulose acetate hemoglobin electrophoresis at alkaline pH (8.6) showed a prominent slow-moving band in S/D/G region and no band in A0 region (Figure 3). Sickling test with 2% freshly prepared sodium metabisulphite was positive (Figure 4). His parents’ HPLCs revealed that his mother was a sickle cell trait (variant peak in S window: 26.1%, Figure 5) and father was an HbD Punjab trait (variant peak in D window: 30.8%, Figure 6).
1. Sickle cell disease (SCD) is the commonest symptomatic hemoglobinopathy in the world with multifarious genotypes and wide phenotypic heterogeneity.
2. HbSD disease is a double heterozygous state with co-inheritance of HBB:c.20A>T and HBB:c.364G>C which produces a severe sickling disorder.
3. Other common double heterozygous states that produce a severe sickling disorder are HbS- beta thalassemia, HbSC, HbSO-Arab and HbS-Lepore diseases.
4. HbSD disease cases usually present early in childhood with infective complications and pain crisis.
5. Hemogram often shows normocytic to macrocytic indices, while peripheral blood film can show sickled red cells.
6. Diagnosis is usually made on HPLC and is confirmed by sickling test and parental studies. Molecular confirmation is usually not required.
7. Treatment of HbSD generally a disease aims at relieving symptoms and preventing infections, sickle cell crises and long-term complications. Stem cell transplant is the only potential cure available presently.
8. HbD Punjab is symptomatically severe only with double heterozygosity with sickle cell trait. Individuals with HbD Punjab trait remain clinically asymptomatic.