Complete absence of HbA with presence of 100% HbF beyond fetal period occurs in five genetic disorders: some variants of homozygous β-thalassemia, some cases of double heterozygosity for δβ-thalassemia and classical β-thalassemia, homozygous patients of hereditary persistence of fetal hemoglobin (HPFH), homozygous δβ-thalassemia, and delta/beta not with HPFH. These conditions can be differentiated on the basis of clinical and hematological features:
1. Homozygous β-thalassemia: behaves as very severe anaemia. Less likely in this patient due to history of only 3 transfusions.
2. Homozygous δβ-thalassemia: clinically mild anaemia with reduced MCV & MCH: both parents will be Heterozygous δβ-thalassemia having CBC similar to beta Thalassaemia trait, but with high HbF (5-20%) & HbA2 normal or reduced.
3. Double heterozygosity for δβ-thalassemia and classical β-thalassemia: If Double heterozygosity for δβ-thalassemia and classical β-thalassemia in child HbA2: One parent will be like typical beta Thalassaemia trait while other will be like heterozygous delta beta with high HbF (5-20%) & HbA2 Normal or reduced.
4. Homozygous HPFH: behaves clinically as normal, with normal red cell indices (albeit erythrocytosis and low MCH, MCH in some) and HbF 10 - 100%. Parents will be having heterozygous HPFH with normal red cell indices and 10 - 35% Hb F.