Clinical features and molecular analysis in Thai patients with HbH disease.

We studied the alpha-globin gene abnormalities, the clinical features, hematologic values, growth assessment, transfusion therapy, and serum ferritin levels of patients with hemoglobin H (HbH) disease in southern Thailand. HbH disease in 83 of the 147 patients was the deletional type of HbH. The remaining 64 patients was the nondeletional type of HbH disease. All 83 patients with the deletional type were double heterozygotes of alpha(0)-thalassemia and alpha(+)-thalassemia. The Southeast Asian type of alpha(0)-thalassemia accounted for 98% of the Thai patients with HbH disease and the Thai type of alpha(0)-thalassemia made up the rest. A 3.7-kb deletion accounted for 91% of alpha(+)-thalassemia, and a 4.2-kb deletion made up the rest of the deletional type. In patients with nondeletional type of HbH disease, the Constant Spring variant was the majority of the disease. Newborns with a nondeletional genotype had higher mean corpuscular volume, had higher mean corpuscular hemoglobin, had higher red blood cell distribution width, had lower mean corpuscular hemoglobin concentration, and had higher proportions of Hb Bart's than those with a deletional genotype. Twenty-one percent of children with HbH disease had growth deficiency. A genotype-phenotype correlation was found; patients with the nondeletional type of HbH disease had more symptoms at a younger age, more severe hemolytic anemia, more growth deficiency, more dysmorphic facial features, larger spleens, larger livers, and higher serum ferritin levels and required more transfusions than patients with deletional HbH disease.

Glucose-6-phosphate dehydrogenase variants associated with favism in Thai children.

In a study conducted at Songklanagarind Hospital in the south of Thailand, the subjects were 225 patients (210 boys and 15 girls) with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Favism was found in 3.6% of the G6PD-deficient children. Approximately one half of the G6PD-deficient patients with favism were younger than 2 years. Sudden onset of anemia was found within 1 to 3 days after ingestion of dried fava beans. The classic features of favism, which are pallor, hemoglobinuria, and jaundice, were detected in all cases. To characterize the known G6PD mutations in Thai children, molecular analysis was performed for 8 G6PD-deficient children with favism by a combination of polymerase chain reaction-restriction fragment length polymorphism analysis and amplification refractory mutation system analysis. The G6PD variants in these children were G6PD Kaiping 1388,G-->A; G6PD Mahidol 487,G-->A; G6PD Viangchan 871,G-->A; and uncharacterized mutation with silent mutation 1311,C-->T.

Molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) variants in the south of Thailand and identification of a novel variant (G6PD Songklanagarind).

Two hundred and twenty-five G6PD-deficient subjects in Songklanagarind Hospital in the south of Thailand comprising 210 males and 15 females were studied. Neonatal jaundice was detected in 85% of these patients. Acute hemolysis related to infection was detected in 17.3% of the G6PD-deficient subjects. Drug-induced acute hemolysis was detected in 1.8% and favism was observed in 3.6% of G6PD-deficient patients. The molecular analysis was performed on 134 G6PD-deficient individuals by a combination of PCR-RFLP, multiplex polymerase chain reaction by multiple tandem forward primers and a common reverse primer assay (MPTP) and DNA sequencing to characterize the mutations of the samples with abnormal MPTP bands. We found 10 different missense G6PD mutations and the three most common variants were G6PD Viangchan 871,G-->A (31.3%), G6PD Kaiping 1388,G-->A (20.1%) and G6PD Mahidol 487,G-->A (17.2%) followed by G6PD Canton 1376,G-->T (9.7%), G6PD Union 1360,C-->T (2.2%), G6PD Gaohe 95,A-->G (1.5%), G6PD Quing Yuan 392,G-->T (0.7%), G6PD Mediterranean 563,C-->T (0.7%), G6PD Songklanagarind 196,T-->A (0.7%), silent mutation 1311,C-->T (6.7%), and uncharacterized variant (9%). A novel missense mutation at codon 196, TTC-->ATC in exon 4 of the G6PD gene predicting a single amino acid substitution, Phe66Ile was identified and we designated this novel class II variant as G6PD Songklanagarind. The G6PD variants among the Thais in the southern part are heterogeneous and G6PD Viangchan, Kaiping, Mahidol, and Canton variants account for about 78% of the cases. Our findings provide some evidence that G6PD Viangchan and Mahidol are common Southeast Asian variants and support the theory of genetic drifts throughout Southeast Asia.

Hb G-Makassar [beta6(A3)Glu-->Ala; codon 6 (GAG-->GCG)]: molecular characterization, clinical, and hematological effects.

We report a Thai family in which five members are Hb G-Makassar heterozygotes and one member is, in addition, a heterozygote for beta0-thalassemia (IVS-I-1, G-->T). We confirm that the previously presumed mutation at codon 6 of the beta-globin gene is GAG-->GCG. Hb G-Makassar heterozygotes are asymptomatic and hematologically normal. The Hb G-Makassar/beta0-thalassemia compound heterozygote has features of thalassemia minor. A simple and rapid polymerase chain reaction-restriction fragment length polymorphism for the detection of Hb G-Makassar is described.