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The case of an eight years old African boy who suffers from sickle cell-thalassemia is presented. In the course of the disease frequent pain attacks occurred within the abdomen and extremities, recently also within the trunk. Local pain, at some occasions in combination with local swelling and always positive laboratory parameters for inflammation, hindered a solely clinical differentiation between bone infarcts and osteomyelitis. Bone scintigraphy, eventually in combination with bone marrow scintigraphy, can assist the clinician in the differentiation of aseptic bone infarcts versus secondary osteomyelitis. Based on the presented case scintigraphic results for bone infarcts, osteomyelitis and special scintigraphic pattern seen in sickle cell disease are presented. Furthermore, problems regarding the interpretation of the scintigraphies in relation to the delayed time after the beginning of pain attacks are discussed.

A 7 year old Kurdish girl presented with a cerebral infarction and a resulting hemiparesis following a blood transfusion. Examination of the blood film suggested sickle cell anaemia. However a simultaneously carried out haemoglobin electrophoresis showed haemoglobin S and haemoglobin D. The diagnosis of haemoglobin SD disease was thereby established. This kind of haemoglobin disorder usually shows a mild clinical manifestation. According to our knowledge such serious cases have not been published before. With this disease the main emphasis is on the prevention of recurrent cerebral infarctions bay a long-term transfusion programme whereas the effects of the cerebral infarction are treated in the usual way.

At present more than 300 children and adolescents with Thalassaemia major are living in the FRG. The purpose of this project is--for the first time--to apply a standardized therapy protocol to these patients, to prove its effectivity and study side-effects. The multi-center study started in April 1991. The therapy is based on periodical transfusion of erythrocytes in order to keep haemoglobin (Hb) concentration (= basic Hb-value) above 10.5 g/dl, and daily application of Desferal, 40 mg/kg bw s.c. for iron elimination. Until Nov. 30, 1991 74 patients from 31 different childrens hospitals entered the study. Preliminary results after evaluation of the basic questionnaires can be summarized as follows: 1. The majority of patients if not too old to highly profit from improvement of therapy; 2. In 40.9% of these patients HbF concentration was higher than 15%, which indicates a suboptimal transfusion therapy; 3. At least 30% of patients need intensified iron elimination. Even these preliminary data demonstrate the necessity to improve the therapy of Thalassaemia major in Germany. The goal is to include all affected patients in the study and so optimize long term results concerning quality of life and prognosis.

Clinically, homozygous beta-thalassaemia is characterised by a severe anaemia requiring regular transfusion therapy in most patients. However, there is a marked clinical variability ranging from this severe picture to the virtual absence of symptoms and haematological abnormalities. Biochemically, beta-globin synthesis in the erythroid precursors of the bone marrow is reduced or absent resulting in a relative excess of insoluble alpha-globin chains and dyserythropoiesis. The molecular genetics of this disorder is highly variable involving a multitude of different mutations of the beta-globin gene. These mutations can inactivate gene expression at all levels on its way from DNA to mature haemoglobin. The clinical picture is largely determined by the type of mutations inherited. Additionally the degree of alpha-globin chain excess can be influenced by the co-inheritance of alpha-thalassaemia or mutations resulting in the hereditary persistence of fetal globin synthesis (HPFH). This review discusses the relationship between the molecular defect and the clinical picture of patients with beta-thalassaemia.

An Italian boy with homozygous beta-thalassemia showed a shortening of transfusion intervals at the age of three years. He had a positive direct antiglobulin test (DAT) because of C3d-loaded red blood cells without any detectable erythrocytic antibody. Serologic investigations indicated a recent EBV infection. Pool immunoglobulin fluorescence test (PIT) revealed a loading of red blood cell membranes with antigens. Oral prednisone therapy did not show any effect. After a single infusion of 400 mg immunoglobulin per kg body weight decrease of hemoglobin concentration slowed down to the rate before crisis. DAT and PIT became negative. The immune hemolytic crisis was possibly due to erythrocyte loading with EBV antigen that caused activation of the alternate complement pathway. Detection of antigen loaded red blood cells by PIT suggested a immunoglobulin therapy in order to coat the structures promoting hemolysis. Thus, a positive PIT seems to be a criterion for successful application of immunoglobulins in immune hemolytic anemia.

alpha-Thalassaemia is a disturbance of the alpha-chain synthesis of the haemoglobin, which occurs mostly in the Far East. On account of the total absence of alpha-chains, the homozygous form is considered to be fatal. However, beta and lambda chains exist abundantly. Abortion, intrauterine or perinatal death are the results of the extreme anaemia (Hb-Bart's syndrome), despite modern intensive medical care. The prenatal diagnosis is possible by: 1. DNA analysis of material obtained by chorion villi sampling or culture of fibroblasts, when a risk of re-occurrence is known to the physician. 2. Hb-electrophoresis from foetal blood in cases of hydrops of uncertain origin. When the diagnosis of this fatal disease is established, there is no foetal indication for delivery by Caesarian section.

Owing to the fact that Germany has become the domicile of a great number of aliens from Mediterranean countries, an increasing number of thalassaemia cases have been reported and given cause for a thorough investigation. Since thalassaemia minor is a hereditary disease, a special prophylaxis has to take place in case of pregnancy: 1. examination of child's generator, 2. genetic counselling, 3. embryoscopy and extraction of embryonic blood, 4. if thalassaemia is diagnosed, an abortion should be taken into consideration.

A case report is presented of the rare haemoglobinopathy HbS-thalassaemia, type betaS-betathal-O in a Greek family. The special diagnostic features are discussed, with particular reference to the differential diagnosis.

By applying gene technology, great progress has been made in defining the molecular basis of thalassemias. While the prevention of thalassemias through prenatal diagnosis has improved significantly, advances for molecular therapy have been rather limited until now.

Heterozygous classical beta-thalassemia was found in 13 subjects of pure German descent, 11 of them from the Bergische Land (NW Germany) during the past three years. Clinically it became manifest in a moderate degree of anemia with marked hypochromia and reduced mean corpuscular volume. The number of red blood corpuscles and the value for serum iron were ascertained to be in the upper limits of normal or raised. The diagnosis of Mediterranean anemia was confirmed by hemoglobin electrophoresis with a rise in HbA2 of more than 3%. A slight increase in HbF may also occur. The importance of genetic counseling of thalassemia patients is emphasized. The occurrence of thalassemia even in pure German populations must be increasingly reckoned with.

The haemoglobinopathies are a group of autosomal recessively inherited diseases that are common among populations in the Mediterranean, in Africa and large parts of Asia. In Germany, the immigration of people from those parts of the world has resulted in an increased occurrence in particular of beta thalassaemia. Homozygous patients usually become transfusion dependent during the first year of life as the excess of alpha globin chains in the erythroid precursors causes a most severe dyserythropoietic anaemia. Genetic determinants that diminish the alpha globin chain excess are thus clinically significant. Here, we describe the molecular genetic changes that result in an increased gamma globin gene expression and hende in a binding of alpha globin chains as HbF. We discuss the significance of those changes for the clinical course of beta thalassaemia and for the elucidation of the ontogenetic processes of gene regulation during the perinatal haemoglobin switch.

Musculoskeletal systems of 19 patients with major and intermediate beta thalassemia were evaluated clinically and radiologically. Rheumatic findings were determined in 17 patients. Symptoms were localized mainly at shoulders, knees, and ankles. The most frequent signs were pain, inflammation, crepitance, radiologically determined periarticular cystic formations, and osteoporosis. Joint involvement was in the nature of non-erosive, destructive osteoarthropathy. It was also found that the symptoms in males were more severe and numerous than in females. No difference was observed between major and intermediate thalassemic cases. There was no correlation between the therapy and the findings. Upper limb involvement was almost equal to the lower limb involvement in contrast to a previous study.

The organization of genes of animal cells is discussed. The genes for 5S-RNA, rRNA and for histones are examples of the organization of repetitive genes. The interruptions of the coding sequence of the mouse beta-globin gene illustrates the split nature of many eukaryotic genes. It is shown that changes in the organization of genes do occur during the normal development of an organism. The methods used for the analysis of gene structure are of great importance for elucidation of the molecular basis of genetic diseases like the thalassemias.

A total of 2672 cases with thalassemia syndromes observed in the period from 1 January 1968 to 30 April 1974 are classified according to type of thalassemia and the patient's country of origin. During the past 15 years some 10 patients annually with classical heterozygous beta-thalassaemia have been found to be of purely Swiss origin. Due to increased immigration from Mediterranean countries the Swiss patients represent only 2.6 percent of all cases at the present time, a marked decrease from the earlier 30 percent. Since 1968 2260 cases of thalassemia syndrome have been found in Italian patients. Smaller groups of patients originate from Greece, Spain and Turkey. Homozygous beta-thalassemia was observed in 56 cases. Ranking third among thalassemia syndromes is the Hb Lepore trait found in 16 cases. The increase in thalassemia syndromes due to population migration over the past 10 years has resulted in the finding of rare types in Switzerland: 8 patients with HbS-beta-thalassemia, 2 with HbC-beta-thalassemia, 3 cases of HbH-alpha-thalassemia and 2 cases of Hb Bart's-alpha-thalassemia are reported. The difficulty of diagnosing deltabeta-thalassemia and alpha-thalassemia is emphasized.

Subcutaneous continuous infusions of deferoxamine were administered to 28 children with thalassaemia major. Longitudinal growth beyond the eleventh year was favourably influenced. The normal growth spurt during puberty was not demonstrable in six patients (three boys and three girls) during their puberty. Taking into account standard height allowing for parents' height, prospective final height and ethnic origin, the treatment favourably influenced longitudinal growth in 26 of the 28 children.

After an extensive educational campaign for the medical community in the area of the Westf. Wilhelms-University Münster five pregnancies at risk for sickle cell anemia and thalassemias were investigated during the first trimester of pregnancy. Following chorionic villi sampling in one case a sickle cell anemia and in two other cases a beta-thalassemia could be excluded. In two additional cases a homozygous beta-thalassemia was proven and in one of the cases the first trimester diagnosis was confirmed in the second trimester by fetal blood sampling. Because of the migration patterns in Europe there is currently a considerable demand for prenatal diagnosis of beta-thalassemias in West-Germany after proper information of the population at risk.

This report deals with a large German family in which 12 carriers of the trait had the characteristic hematologic abnormalities of thalassemia minor. Among these are increased red cell count, decreased hemoglobin content, microcytosis and marked hypochromia in the presence of normal or increased serum iron levels. Thalassemia should always be considered if these hematologic abnormalities are found. It probably occurs more often in central Europe than thought of hitherto.

Six children, 2 1/2 to 6 years old, with homozygous beta-thalassemia underwent partial splenectomy as indicated by splenomegaly and high blood transfusion requirement. A marked reduction of blood requirement has been achieved in 2 children with an annual blood transfusion volume up to 150 ml per kg body weight. The other four children required total splenectomy as blood requirement remained high and significant splenomegaly developed within few weeks after the partial splenectomy. The immunological function of the spleen residue remains still controversial and needs further evaluation. Partial splenectomy might be indicated therefore only in selected children with homozygous beta-thalassemia.