E.N.T. complications in thalassaemia major.

Twenty-six cases of thalassaemia major have been investigated for E.N.T. complications. Twelve (46 percent) had significantly problems requiring surgery. Since the prognosis of the disease is improving dramatically, these patients should not be denied treatment. bony hypertrophy of the turbinates was a noticeable feature in the untreated group and does not seem to have been described before.

Incidence of -thalassaemia trait among Cypriots in London.

The incidence of beta-thalassaemia trait among Cypriots in London is about 14%, and the birth rate of children with thalassaemia major is 0.6%. The high incidence of the beta-thalassaemia gene among Cypriots suggests the desirability of screening Cypriot school-leavers for thalassaemia trait and following up any incidentally discovered cases with family studies and genetic counselling.

Iron chelation using subcutaneous infusions of diethylene triamine penta-acetic acid (DTPA).

The iron chelating ability and potential toxicity of subcutaneous infusions of the calcium and zinc salts of diethylene triamine penta-acetic acid (DTPA) have been assessed in metabolic balance studies in 2 iron-loaded thalassaemic patients. Infusions of calcium DTPA were locally well tolerated and the drug was as effective as desferrioxamine in mobilising iron. However, daily infusions in the 1st patient also produced symptomatic zinc depletion which could not be controlled by simultaneous oral zinc supplements. Zinc DTPA proved ineffective as an iron chelator, but zinc balance could be maintained in the 2nd patient by combining intermittent (every 4 d) use of calcium DTPA with oral zinc supplements. Combined studies with desferrioxamine and calcium DTPA showed the drugs to have additive effects, probably as a result of the chelation of iron from different body sites.

Family studies of red-cell metabolism of pyridoxine in beta-thalassaemia.

Red-cell conversion of pyridoxine to pyridoxal phosphate was measured in 12 families with thalassaemia and 2 normal families. A strong familial pattern was demonstrated and the evidence suggested that the rate of red-cell conversion of pyridoxine is an independently inherited characteristic.

Abnormal red-cell metabolism of pyridoxine associated with beta-thalassaemia.

Red-cell conversion of pyridoxine to pyridoxal phosphate was studied in control subjects, and patients with heterozygous and homozygous beta-thalassaemia. In 7% of control subjects the rate of pyridoxine conversion was well below the range found in the other control subjects (5.0-8.6%, mean 6.5%/g Hb x 10(-2)) but in heterozygous beta-thalassaemia was below that range in 63% of the patients. The conversion rate was also slow or borderline in the majority of patients with severe transfusion-dependent homozygous beta-thalassaemia, in spite of the presence of some donor cells; but was normal, or fast as in other anaemias, in all but one patient with mild homozygous thalassaemia. There was a much higher incidence of a slow conversion rate in the parents of the severe homozygotes than in parents of the mild homozygotes, illustrating the familial pattern. This supports our view that the red-cell conversion rate of pyridoxine is an inherited characteristic, independent of thalassaemia. The cause of a reduced rate of pyridoxine conversion was investigated. The increase to a normal rate following riboflavin ingestion suggests a defect in the activity of the flavin mononucleotide (FMN)-dependent pyridoxine phosphate oxidase.

Immunogenetic factors in thalassemia and hepatitis B infection. A multicentre study.

Geographical variations in the prevalence of hepatitis B infection were found in association with an increased opportunity of exposure to this virus in patients with homozygous beta-thalassemia in Cyprus, Greece, Sardinia and the United Kingdom. No association was found between the Gm phenotype of the individuals investigated and susceptibility to hepatitis B virus using HBsAg as a marker, or the ability to make antibody to it. Variation in the distribution of Gm haplotypes does not appear to be a feasible explanation for variation in anti-HBs and HBsAg frequencies in a series of highly transfused populations.

Expression of the beta-thalassemia gene in the first trimester fetus.

To determine whether beta-thalassemia can be detected in the fetus, blood was obtained from abortuses of normal mothers and of mothers with beta-thalassemia trait. The red cells were incubated with radioactive leucine and the globin chains were analyzed by radiochromatography. Two independent methods were utilized to correct the results for contamination by maternal radioactive beta-chain, and the corrected beta/gamma ratios were compared to a previously established range of normal fetal beta/gamma synthetic ratios obtained by similar measurements in pure fetal cells. In the erythroid cells of three fetuses from mothers with beta-thalassemia trait, the beta/gamma synthetic ratio was normal in two. The third had a beta/gamma ratio of 0.04 at 10 1/2 weeks, a 50% reduction, consistent with fetal beta-thalassemia trait. Two other fetuses, derived from parents both of whom had beta-thalassemia trait, were also studied. One had a beta/gamma ratio of 0.029 at 8 weeks, a 65% reduction, also consistent with beta-thalassemia trait. The cells of the other had a ratio of essentially zero at 11 weeks, highly suggestive of homozygous beta-thalassemia. Although further experience will be needed to distinguish the homozygous and heterozygous states reliably, it now appears that the beta-thalassemia gene is expressed in the first trimester. Therefore these data suggest that the antenatal diagnosis of beta-thalassemia is becoming an attainable goal.

Prenatal diagnosis of hemoglobinopathies. A review of 15 cases.

We attempted prenatal diagnosis of hemoglobinopathies in 15 cases--11 for beta-thalassemia and four for sickle-cell disease. Fetoscopy was used in seven cases, and placental aspiration in eight. One premature labor, with fetal loss, followed placental aspiration. Globin synthesis was assessed by incubation of samples with 3H-leucine and chain separation on carboxymethylcellulose columns. Homozygous disease was predicted in two pregnancies, which were interrupted, and the diagnosis confirmed. In one case homozygosity was suspected. A repeat test was advised but not accepted. The fetus had thalassemia trait. One pregnancy was interrupted despite our prediction of thalassemia trait. Eight pregnancies went to term. Seven predictions that the infants would not have homozygous disease were confirmed. One prediction of sickle trait proved to be sickle-cell disease. Although prenatal diagnosis of hemoglobinopathies is feasible, the present frequency of fetal loss and diagnostic error indicates need for improvement.