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Hemoglobin (Hb) gene disorders are one of the most common inherited diseases in Taiwan, which include α-thalassemia, β-thalassemia, and Hb variants. In this study, we collected and analyzed mutations found in 930 patients with Hb gene disorders except Hb Bart’s Hydrops and β-thalassemia major. The patients included 650 cases of α-thalassemia, 225 cases of β-thalassemia, 9 cases of α-thalassemia combined with β-thalassemia, and 46 cases of Hb variants or Hb variants combined with α-thalassemia or β-thalassemia. The most common type of α0-thalassemia and α++-thalassemia mutations in our study were the SEA type deletion and the α3.7 deletion, respectively; the most common β-thalassemia mutation was the IVS-2 nt 654 C→T mutation; and the most common Hb variant was the HbE. We compared the relationships between genotype and hematological phenotypes of various Hb gene disorders and found that different genotypes of α0-thalassemia have similar hematological features. In conclusion, the results of our study provide data of the complex interaction of thalassemias and Hb variants which might be useful for other researchers in this field. [ABSTRACT FROM AUTHOR]

Patients with β-thalassemia major still suffer growth retardation. After excluding patients with cortisol deficiency, hypothyroidism, hypogonadism, delayed puberty, malnutrition, severe congestive heart failure, and severely impaired liver function, 29 patients were enrolled in this study. Fifteen (52%) patients exhibited growth retardation and underwent two growth hormone (GH) provocation tests. Eight (53%) of the 15 patients had GH deficiency and were subsequently treated with subcutaneous recombinant human GH (Genotropin, Pharmacia Corporation, Sweden). Growth velocity increased from the pretreatment rate of 3.1±0.4 cm/year to 7.1±1.6 cm/yr (p<0.001) after 1 year and to 6.8±1.3 cm/year (p<0.001) after 2 years. Patients with growth retardation had lower insulin like growth factor-1 (p=0.001) and insulin like growth factor binding protein-3 (p=0.003) levels than those without growth retardation. In patients with β-thalassemia major, growth retardation is a common complication and GH deficiency plays an important role. Thalassemic patients with GH deficiency can safely increase their growth velocity with recombinant human GH for2 years; however, the effect on final height still needs to be determined. [ABSTRACT FROM AUTHOR]

β-Thalassemia is one of the most common genetic diseases in Taiwan. The most common mutations of β-globin are point mutations, and six mutations account for over 90% of cases. Less than 5% of the cases with β-globin gene deletion result in β-thalassemia minor. The mutational type of the deletion is not clear in Taiwanese. We used polymerase chain reaction (PCR)-based methods to detect the breakpoint junctions of different deletional types of β-thalassemia. In total, six cases of clinically suspected deletional type of β-thalassemia were studied. The results showed that there were three types of deletions in these cases: two cases each for hereditary persistent fetal hemoglobinemia (HPFH) of the Southeast Asian (SEA) type, HPFH of the Yunnanese type, and γG+(γAδβ)0 deletions, respectively. The clinical features of these deletional mutations are milder than the βo types of the point mutation. The patients with compound heterozygous mutations of the point mutation and the deletional mutation are always transfusion independent. [ABSTRACT FROM AUTHOR]

Abstract beta-Thalassemia, a hematologic disorder characterized by the deficiency or the absence of beta-globin production, is the most widespread inherited disorder in the world; it is also common in Taiwan. We studied 38 patients in central Taiwan with beta-thalassemia major, using amplified created restriction site analysis for detection. On analysis, six different point mutations were found among 76 chromosomes, of which 32 chromosomes (42.1%) had a C to T substitution at nucleotide 654, 30 (40%) had frameshift codons 41/42 with four nucleotides (TCTT) deletion, 7 (9.2%) had an A to T substitution at codon 17, 3 (3.9%) had frameshift codons 71/72 (insertion of A), 2 (2.6%) had an A to G substitution at position -28, and 2 (2.6%) had frameshift codons 27/28 (insertion of C). The first two mutations accounted for 62 of the 76 beta-thalassemia mutations in this study. As to mutations in each individual with beta-thalassemia major, the incidence of compound heterozygotes of two different mutations was higher than that of homozygotes of a single mutation (60% vs 40%). Compound heterozygotes of C to T substitution at nucleotide 654 of IVS-2 and frameshift codons 41/42 with four-nucleotide deletion was the most common pattern of beta-thalassemia mutations in each individual (23.7%). Our results were unique compared with those from similar studies performed in southern China. Frequencies of beta-thalassemia mutations found in the current study were assessed and compared with frequencies found in previous studies conducted in northern and southern Taiwan. [ABSTRACT FROM AUTHOR]

Cardiac complications caused by iron deposition are major causes of death in patients with β-thalassemia major. Deferiprone (L1) was found to have greater efficacy at depleting myocardial iron than desferrioxamine (DFX). Furthermore, combined therapy with L1 and DFX produced an additive or synergistic iron chelating effect. We report the successful treatment of severe heart failure in two patients with β-thalassemia major with the combined therapy. Magnetic resonance images showed a marked recovery of signal intensity in the heart, indicating a significant reduction of iron load in the heart. No significant adverse effects were noted. Therefore, combined therapy with L1 and DFX should be considered in patients with β-thalassemia major and cardiac complications. [ABSTRACT FROM AUTHOR]