[Current clinical approaches and gene mutation study of beta-thalassemia major].

Forty-one cases of beta-thalassemia major were assessed for their clinical manifestations and gene mutation. The age distribution was from 1 to 18 years old. Patient's initial clinical symptoms began mostly before 2 years of age (90.2%). Patient's initial hematological data included mean hemoglobin value, 5.8 +/- 1.2 gm/dl, hemoglobin F value, 85.0 +/- 12.1%, hemoglobin A2 value 2.3 +/- 1.8%, reticulocyte count 9.2 +/- 9.0%. Eight different point mutations were characterized. Of these mutations, C to T substitution at nucleotide (nt) 654 of intervening sequence (IVS) 2, accounting for 46.3% of mutant beta-globin genes, is the most common mutation in our series, followed by frameshift codons 41/42 with a four nucleotides (TCTT) deletion for 31.7%; A to G substitution at position -28 of the promotor area for 8.5%; A to T substitution at codon 17 for 6.1%; frameshift codons 27/28 (insertion of C) for 2.4%; G to T substitution at nucleotide 1 of IVS-1 for 2.4%; frameshift codons 71/72 (insertion of A) and IVS-1 3' end TAG-->GAG for 1.2%. The first four mutations account for 92.6% of all beta-globin gene mutations in our series. As to mutations in each individual, the incidence of compound heterozygotes of two different mutations is much higher than homozygotes of a single mutation, 78.0% vs. 22.0%. Compound heterozygotes of C to T substitution at nt 654 of IVS-2 and frameshift codons 41/42 with a four nucleotides deletion is the most common pattern of beta-thalassemia mutation in our patients (41.5%). Patients with beta(0)/-28 beta(+) compound heterozygote mutation had much delayed initial symptoms than beta (0)/beta(0) homozygote mutation, but clinical manifestation may be aggravated when the mutation combined with glucose-6-phosphate dehydrogenase deficiency. Severity of iron overload was significantly correlated with total transfusion amount and patient's age in simple regression analysis (p < 0.001). Splenectomy may effectively prolong transfusion interval, maintain higher hemoglobin level before each transfusion and palliate clinical symptoms (p < 0.01). Iron-chelating agent therapy can effectively lower the total amount of serum ferritin. Higher severity of iron overload correlates with higher incidence of EKG and cardiac abnormalities in patients with beta-thalassemia major.