Thalassaemias.pptx The fundamental defect in thalassaemias is a reduction or absence of synthesis of one of the globin chains.
Download as PPTX, PDF
0 likes12 views
The fundamental defect in thalassaemias is a reduction or absence of synthesis of one of the globin chains. There are two main groups of thalassaemias: Alpha-thalassaernia, where the synthesis of A chains is affected. Beta-thalassaernia, where the synthesis of B chains is affected.
Thalassaemias.pptx The fundamental defect in thalassaemias is a reduction or absence of synthesis of one of the globin chains.
- 2. Thalassaemias The fundamental defect in thalassaemias is a reduction or absence of synthesis of one of the globin chains. There are two main groups of thalassaemias: Alpha-thalassaernia, where the synthesis of A chains is affected. Beta-thalassaernia, where the synthesis of B chains is affected.
- 4. Common Forms Alpha-thalassaemias Beta -thalassaemias Alpha-thalassaemia trait beta-thalassaemia minor (heterozygous state) Haemoglobin-H disease beta-thalassaemia intermedia Haemoglobin-Bart's (hydrops foetalis) beta-thalassaemia major (Cooley's anaemia; homozygous state)
- 6. Genetics In homozygous B-thalassaernia, either no normal B-chains are produced or B-chain production is markedly reduced . The excess ALPHA-chains combine with whatever B, 'Y and D chains are produced, resulting in increased quantities of Hb A2 and Hb F, and at best, a small amount of Hb A.
- 9. Genetics There are four genes for A-chain, two on each chromosome. Deletion of one A-chain gene or both A-chain genes on each chromosome may occur. Deletion of one A-gene from one or both chromosomes produces A-thalassaemia trait. Deletion of three A-genes produces Hb H . If all four genes are absent, there is no A-chain synthesis and only Hb Bart's is present. It is incompatible with life. The infants are either stillborn at 28-40 weeks or die very shortly after birth. They are pale, oedematous, and have large liver and spleen (hydrops foetalis).
- 11. Beta-thalassaemia major (Cooley's anaemia). B-thalassaemia major is the homozygous state of B-thalassaemia. B chain synthesis is absent or grossly reduced In India, common among communities like Sindhi, Punjabi, Gujarat, Parsee. Less common in South India. Anaemia occurs due to combined RBC destruction in the bone marrow (ineffective erythropoiesis) and spleen. Anaemia and poor tissue oxygenation stimulate increased kidney EPO production that further drives marrow erythropoiesis, resulting in increased ineffective marrow activity and the classic bony deformities.
- 12. Clinical Features Severe anaemia (usually develops at 6-24 months of age) and its complications. Growth and development retardation, feeding problems, diarrhoea and irritability. Splenomegaly, at times massive. Hepatomegaly. Bone marrow hyperplasia resulting in deformities of long bones of legs and craniofacial changes (bossing of the skull, prominent malar eminence, depression of bridge of nose, tendency to a mongoloid slant of the eye and hypertrophy of the maxillae, which tends to expose the upper teeth).
- 13. Clinical Features Development of masses from extramedullary haematopoiesis. Paraspinal masses may produce cord compression. Increased risk of thrombosis particularly in patients who are non-transfused or infrequently transfused and in patients who are splenectomised. Deposition of iron in tissues (haemosiderosis) resulting in organ failure. This may be due to increased gastrointestinal absorption of iron and can occur even without exogenously administered iron. Pancreatic haemosiderosis resulting in diabetes.
- 14. Clinical Features Hepatic haemosiderosis resulting in cirrhosis. Cardiac haemosiderosis resulting in arrhythmias, heart blocks and congestive heart failure (primary causes of death). Deposition of iron in various endocrine organs leads to growth hormone deficiency, delayed puberty, hypogonadotropic hypogonadism, impaired glucose metabolism and type 1 diabetes mellitus, osteopaenia, hypothyroidism, and hypoparathyroidism.