Beta-thalassemia

Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta globin gene on chromosome 11, leading to reduced (beta+) or absent (beta0) synthesis of the beta chains of hemoglobin (Hb). Transmission is autosomal recessive; however, dominant mutations have also been reported. Diagnosis of thalassemia is based on hematologic and molecular genetic testing. Differential diagnosis is usually straightforward but may include genetic sideroblastic anemias, congenital dyserythropoietic anemias, and other conditions with high levels of HbF (such as juvenile myelomonocytic leukemia and aplastic anemia). Genetic counseling is recommended and prenatal diagnosis may be offered. Treatment of thalassemia major includes regular RBC transfusions, iron chelation and management of secondary complications of iron overload. In some circumstances, spleen removal may be required. Bone marrow transplantation remains the only definitive cure currently available. Individuals with thalassemia intermedia may require splenectomy, folic acid supplementation, treatment of extramedullary erythropoietic masses and leg ulcers, prevention and therapy of thromboembolic events. Prognosis for individuals with beta-thalassemia has improved substantially in the last 20 years following recent medical advances in transfusion, iron chelation and bone marrow transplantation therapy. However, cardiac disease remains the main cause of death in patients with iron overload

Urinary vanillyl-mandelic acid (VMA) excretion by chronically anaemic children

The 24-hour excretion of VMA by healthy and by chronically anaemic children aged 2-121 years, increased with both age and body weight. When the excretion was related to body weight anaemic children put out almost twice as much VMA as did healthy children. The latter excreted the same VMA per kg. body weight at all ages, but in the presence of chronic anaemia the younger the child the more VMA he excreted. The results are consistent with the concept that hypoxia is associated with increased catecholamine biosynthesis

Blood plasma levels and urinary excretion of ascorbic acid before and after a test dose in children with severe thalassemia

Summary1.The plasma ascorbic acid levels were determined in 22 children with severe thalassemia and in 12 normal children before and after an intramuscular injection of 50 mg. per kilogram of ascorbic acid. In 5 of the normal and 5 of the anemic children the urinary excretion of ascorbic acid before and after the test dose was also investigated.2.Before the injection of the test dose, the plasma ascorbic acid levels were invariably lower in the children with thalassemia than in the normal ones, and especially so in those with considerable splenomegaly. The test dose produced a greater initial rise, followed by a more rapid fall in the plasma levels of the anemic subjects.3.The urinary excretion of ascorbic acid before the test dose was considerably lower than normal in the children with thalassemia. The test dose produced a very similar initial rise in the renal elimination of the vitamin in both the normal and the anemic children, but this was followed by a decline in the rate of excretion which was more rapid in the anemic children. The over-all retention of injected ascorbic acid was considerably greater in the children with thalassemia.4.These observations suggest a mild ascorbic acid deficiency in children with severe thalassemia. The significance of this deficiency is discussed. © 1961 The C. V. Mosby Company

Low mitotic activity of peripheral lymphocytes during the first two years of life

The in vitro response of peripheral lymphocytes to phytohaemagglutinin was investigated in children less than 2 years old, in children 8-13 years old, and in adults. The mean mitotic index in the very young children was about one-half that of older children or adults. Mitotic counts tended to increase with increasing age during the first two years of life. It is suggested that the weaker lymphocytic response to phytohaemagglutinin may be associated with relative incompetence of the cellular immune mechanism in early life