Supa Na-Nakorn

The Pattern of Disordered Haemoglobin Synthesis in Homozygous and Heterozygous β-Thalassaemia*

The rate of globin chain production has been studied in patients with homozygous β‐thalassaemia, heterozygous β‐thalassaemia, haemoglobin E‐thalassaemia, and sickle‐cell‐thalassaemia, and compared with that in non‐thalassaemic individuals. A partial or total deficit of β‐chain synthesis has been demonstrated in all forms of β‐thalassaemia. This results in the production of a large intracellular pool of α‐chains, the kinetics of which have been worked out. The α‐chains in this pool appear to contain haem and are unstable, rapidly becoming associated with the stromal fraction. These findings are examined in terms of the pathogenesis of the anaemia of thalassaemia.

Studies of the Distribution of Haemoglobin E, Thalassaemias and Glucose-6-phosphate Dehydrogenase Deficiency in North-eastern Thailand

DURING our survey in 1963, examinations were made of 1,030 subjects in the provinces of Ubol(rajthani), Khonkaen and Udorn(thani) in north-eastern Thailand. The subjects were villagers, soldiers, hospital patients and prisoners. Haemoglobin types were based on cellulose acetate strip electrophoresis in veronal buffer, pH. 8.6, ionic strength 0.025. Thalassaemia trait was designated to those with Hb A who showed decreased red cell osmotic fragility in a one tube screening method1, hypochromic microcytic red cells and serum iron not lower than 50γ per cent; these persons who had Hb A2, as determined by starch block electrophoresis2,3, higher than 3.1 per cent were further classified as β-thalassaemia traits and the others with 3.1 per cent Hb A2 or lower as α-thalassaemia traits. In Ubol glucose-6-phosphate dehydrogenase (G-6-PD) activity was screened with Motulskys technique4, but in Khonkaen and Udorn a spot test was carried out according to Fairbanks and Beutler5.

The Thai variant and the distribution of alleles of 6-phosphogluconate dehydrogenase and the distribution of glucose 6-phosphate dehydrogenase deficiency in Thailand

The samples were taken from 3185 subjects from ten provinces throughout Thailand. In 1577 males the frequency of glucose 6-phosphate dehydrogenase deficiency was 11.98%. In the far south the gene frequency was 2.83%; in the remainder of the country the frequency did not vary significantly about a mean of 13.76%. The deficiency is of a severe type. The G6PD of all of the nondeficient individuals had the electrophoretic mobility of type B. The mean frequency of the A/B electrophoretic phenotype of 6-phosphogluconate dehydrogenase is 8.47%. The maximum frequency was in central and southern Thailand with a decline to the north and northeast. A variant form of 6-PGD, referred to as the Thai variant, has been found in which two additional electrophoretic components migrate anodally to the normal A band, confirming that the molecule is at least a dimer. The hypothesis is advanced that erythrocyte 6-PGD is determined by two genetic loci, only one of which is translated in leukocytes.

Haemoglobin J-Bangkok: a clinical, haematological and genetical study.

A Thai family with haemoglobins A + J‐Bangkok in nine persons is described. This rare abnormal pigment had identical electrophoretic mobility to other haemoglobins J, but, as α2β256Asp, is not similar to any previously described haemoglobin. Carriers of this haemoglobin were clinically and haematologically normal except for the presence of 47.4–67.2 per cent Hb J. It was also possible to follow the increment of Hb J‐Bangkok from 16.15 per cent in the cord blood to 46 per cent at 2½ months and to 55.18 per cent at 1 year of age. One person is believed to harbour both an α‐thalassaemia and Hb J‐Bangkok genes without evidence of interaction.

Incidence of haemoglobin Thai: a re-examination of the genetics of α-thalassaemic diseases

Haemoglobin (Hb) H disease is a mild to severe a-thalassaemic disease, characterized by the haemoglobin types of A + H and intra-erythrocytic inclusion bodies. The latter are aggregated masses of Hb H (/I4). This disease has been reported from many parts of the world, but is especially common among the Thai and the Chinese. Over 400 patients have been examined by us, not including more cases in the Department of Paediatrics of this hospital. The genetics of Hb H disease is peculiar, Hb H being not detectable in either parent in the majority of cases. It has been suggested (Wasi, Na-Nakorn & Suingdumrong, 1964; Huehns, 1965) that this disease results from double heterozygosity between a severe a-thalassaemia gene (a-thal,) and a milder allele (a-thal,). a-thal, leads to a complete, while a-thal, to a partial, suppression of a-chain synthesis. Homozygosity for a-thal, results in Hb Barts hydrops foetalis in which no Hb A is synthesized (Weatherall, Clegg & Wong, 1970; Todd et al. 1970). Further evidence (Na-Nakorn et al. 1969; Na-Nakorn & Wasi, 1970) supports the hypothesis of a-thal, and a-thal,. A haemoglobin, slower than Hb A, in starch-gel electrophoresis in alkaline pH, in association with a-thalassaemic diseases, was first reported from this laboratory in 1967 (Wasi et al. 1967) and again in 1968 (Wasi et al. 1969). This was found by Dr E. R. Huehns to be an a-chain variant, and has been named Hb Thai (Wasi, 1970b). Hb Thai constitutes only 1-2 % or less of the total haemoglobin. Thus it often escapes detection. The reason for its presence in such a small amount is yet to be shown, but it is very likely that this is due to decreased synthesis. Hb Thai gene, with almost complete suppression of a-chain synthesis, thus would have an a-thalassaemia-like effect. Double heterozygosity between Hb Thai gene and an a-thalassaemia gene should lead to a Hb H disease with the presence of a small amount of Hb Thai. The prevalence of Hb Thai among a-thalassaemic diseases has never been reported before. This should be very important in understanding the genetics of a-thalassaemia. We wish to report the incidence of Hb Thai among patients with Hb H disease. b

IDENTIFICATION OF SLOW-MOVING HÆMOGLOBINS IN HÆMOGLOBIN H DISEASE FROM DIFFERENT RACIAL GROUPS

Abstract Slow-moving haemoglobin components have been found in small amounts in some patients with hœmoglobin H disease from Greece, Thailand, Malaysia, and Hong Kong. Chemical analysis indicates that in each case the abnormal haemoglobins are identical to haemoglobin Constant Spring (Hb CS), a variant with an elongated α-chain.

Hereditary Persistence of Foetal Haemogloblll in a Thai Family: The First Instance in the Mongol Race and in Association with Haemoglobin E

Summary. Hereditary persistence of foetal haemoglobin is described in a Thai family. The AF heterozygotes were healthy and had normal haematological findings except the decrease in haemoglobin A2 level and the presence of a large amount of haemoglobin F. The latter, comprising 21–22 per cent, is higher than in the Greek but lower than in the Negro counterparts. Three persons, who were heterozygous for both haemoglobin E and high F genes, were not anaemic but had numerous target‐erythrocytes; haemoglobin E constituted 40 per cent, the rest being haemoglobin F. Acid‐elution staining revealed haemoglobin F in every red cell in both AF and EF heterozygotes. The absence of haemoglobin A in the latter suggests allelism between this type of hereditary persistence of foetal haemoglobin and haemoglobin E or β‐structural gene.