How Does Thalassemia Affect the Skeletal System - Essay Example

Thalassemia Impact on Skeletal System Thalassemia Impact on Skeletal System Introduction Thalassemia is a Greek word for sea blood that is, the place of origin of where the disorder was first discovered among people living around the Mediterranean Sea (Ortner, 2003). To date, the cases of Thalassemia are still high in these regions, and the genes carrying the disorder continue being reported in people with their ancestral lands around the Mediterranean, the Middle East, and Southern Asia. Thalassemia affects both men and women and occurs in an estimated 1 of every 100000 individuals worldwide. The essay examines the effects of Thalassemia on the skeletal system and what its pathology affects. Thalassemia is a hereditary disorder characterized by a diminished or a malfunction of the production of hemoglobin; a blood protein that transports oxygen to the tissues, which results from the mutation of the manufacture of hemoglobin primarily because of the abnormality of the bones and the enlargement of the spleen. Anemia is a good example that portrays severe cases of Thalassemia; bone and growth deformities, defects and hemosiderosis (Barber & Stringer, 2011). The most common Thalassemias are alpha-Thalassemia and beta-Thalassemia whose frequency of occurrence is around 1.7% worldwide. Alpha-Thalassemia comes from the abnormal production of the α-globin chain while β-Thalassemia is from the β-globin chain (Barber & Stringer, 2011). Alpha-Thalassemia affects mainly people from Africa and South-East Asia while beta-Thalassemia is prevalent among people from the Mediterranean, Africa, and South-East Asia. The predominance of β-Thalassemia is higher in areas where malaria is or was once an endemic. The Effects on the Skeletal System The Axial Skeleton The Calvaria Severe changes occur on the calvarium due to porotic hyperostosis as shown in figure 1 below. This manifests extensively on the frontal portion including the inferior portion, the parietals and the squamous of the occipital through porosis (Lagia et al., 2007). Due to Thalassemia, patients often experience extensive pitting in the posterior portion of the skull, which includes the parietal and occipital bones as shown in figure 3. There is also mild pitting of the frontal bone and the orbital roof as demonstrated in figure 2. For this reason, the cranial bones become thicker than usual, wavering from typical 4.5mm to a maximum of 10mm in thickness (Filon et al., 1995). The expanded diploe can be seen on the external surface, which becomes eroded over time. The trabeculae of the diploe become increasingly reduced in number, accompanied by the thickening and radial arrangement of the trabeculae that are left; hence, forming a distinctive hair-on-end appearance as shown in figure 4. Figure 1 showing the entire proliferation of the calvarium (Lagia et al., 2007) Figure 2 showing pitting in the frontal-parietal lobe (Manzon, 2007) Figure 3 showing porotic hyperostosis in the parietal bone (Manzon, 2007) Figure 4 showing the hair-on-end appearance (Manzon, 2007) The maxillae Thalassemia also has a significant impact on facial bones and the overall appearance of the face. Frontal bossing occurs starting from the infant stage. The maxilla and zygoma become thick and coarse resulting in the patient having a mongoloid appearance. Since both the maxilla and mandible are involved, it results in an uncontrollable characteristic of the popping up of the teeth and the misalignment of the jaws, thus creating a rodent-like appearance, which is typical for children suffering from Thalassemia. Therefore, the upper incisor teeth protrude out in such cases as shown in the figure below of the maxillae of Thalassemia patient. Figure 5 showing the uncontrollable sprouting of teeth and a misaligned dental structure (Lagia et al., 2007) The ribs The ribs of Thalassemia patients are characterized by widespread lesions in the ribs (Lagia et al., 2007). A large part of the posterior portion of the ribs broadens and reticulates due to the decline of the total mass of the trabecular and the cortical bone. Thus, the remaining trabeculae arrange themselves along the stress lines extending the posterior section of the ribs. It is the porosis of the vertebrae, reduced height, increased width, and the cupping of the endplates that leads to the characteristic fish-vertebrae feature as shown below. Figure 6 showing the widened ribs (Lagia et al., 2007) The Appendicular Skeleton The Long and Short Bones The long bones typically show a marked extension of the medullar cavity together with the thinning of the cortex that looks like a network or web. Usually, it has a noticeable distended vascular foramina containing hyperplasic marrow. It also showcases a striking porosity and a distinctive flask-shaped deformity of the metaphyseal portion of the tubular bones known as Erlenmeyer flask deformity as shown in figure 7 (Manzon, 2007). There is also notable osteoporosis and osteopenia as shown in figure 9 (Manzon, 2007). Other effects of Thalassemia on the long bones include observable weakness of the bones, multiple Harris lines (Figure 8), delayed epiphyseal closure and a typical decline in growth, which results in dwarfism (Manzon, 2007). The human limbs, especially those of children, usually present an enlargement of the metacarpals, metatarsals and phalanges resulting in the emergence of a diagonal crossing trabeculae and highly-webbed thin cortices that in the end leads to the creation of a honey-comb pattern of the hand and foot short tabular bones (Manzon, 2007). Figure 7 showing Erlenmeyer flask deformity (Manzon, 2007) Figure 8 showing the multiple Harris lines (Manzon, 2007) Figure 9: the middle bone shows osteopenia (Manzon, 2007) The Pathology of Thalassemia and It Affects Thalassemia results from the abnormal synthesis of hemoglobin. The two broad categories of Thalassemia are categorized based on of hemoglobin, which can either alpha hemoglobin chain or the beta hemoglobin chain (Ortner, 2003). The beta thalassemia affects people from mainly central and eastern Mediterranean such as Italians, Greeks and North Africans except the French and Spaniards (Ortner, 2003). The alpha thalassemia, on the other hand, affects people in the rest of the world such as India, Thailand, Malaysia, China and the Philippines (Ortner, 2003). The alpha thalassemia results from the deficiency in the production of the α-globin chains that leads to an overproduction of β-globin chains. The synthesis of the α-globin chain is controlled by two genes on each of chromosome 16 (“Epidemiology and Pathophysiology”, 2015). The deficiency in the synthesis results from the deletion of these genes. On the other side, beta thalassemia results from the deficient synthesis of β-globin chains resulting in the excess production of α-globin chains. One gene controls the production of the β chains on each chromosome 11 (“Epidemiology and Pathophysiology”, 2015). Β-thalassemia comes about due to the mutation of the gene on these chromosomes. The homozygous presentation of Thalassemia is called thalassemia major while its heterozygous expression is called thalassemia minor. Thalassemia minor usually has no clinical manifestations without any changes in the skeletal system. The thalassemia major causes numerous deaths in infants and children and reduces the lifespan of adults. In thalassemia major, various bone changes occur that are noticeable after the first year of life unlike in thalassemia minor. Many thalassemia major patients experience an imbalance in the bone mineral turnover; hence resulting in osteoporosis because of diminished bone mineral density, thus leading to stunted growth and delayed bone age Perisano et al., 2012). Moreover, an excessive deposition of iron on the mineralization fronts and osteoid surfaces of the bones also occurs resulting in skeletal abnormalities (Perisano et al., 2012). Conversely, when the iron is incorporated in calcium hydroxyapatite, it affects the growth of crystals resulting in defective mineralization (Perisano et al., 2012). Thalassemia also results in nutritional insufficiencies in those it affects, and this often contributes significantly to the continued worsening of the condition and increased abnormalities of the bones. An example of the nutrient deficiency is the vitamin C that impairs the activation of the osteoblast and thus reduces the production of collagen (Perisano et al., 2012). Vitamin D deficiencies also result in weaker bones and thus patients with thalassemia usually end up having little to no physical activity due to disease complications. This results in more fragile bodies and ultimately reduced bone formation. The hormonal imbalances leading to conditions such as hypogonadism (Hamidi, 2012) are also common in people with thalassemia and can result in reduced bone growth. However, this can be treated using endocrine therapy. The most efficient treatment for thalassemia is the bone marrow transplant. Other treatments that can lessen the impact of the disease include blood transfusion, splenectomy and iron chelation. Conclusion Thalassemia is a genetic disease that results in an abnormal production of hemoglobin. It results in many bone and skeletal abnormalities in thalassemia patients. The disorder often affects the skull significantly, which is manifested by the thickening and extensive pitting. The maxillae also show a significant difference from those of a healthy person. The face appears also to be mongoloid in nature while the teeth have a rodent-like appearance due to misalignment of the jaws. The disorder also affects the ribs, long bones, and short bones significantly. Ultimately, thalassemia is of two main types, the alpha thalassemia, and beta thalassemia and both have adverse effects on the life of the patients and can even result in death, in addition to, the abnormal development of bones and growth, and reduced lifespan. However, the disorder can be controlled through treatments such as regular blood transfusions, iron chelation, endocrine therapy, splenectomy and bone marrow transplants. References Barber, W. H., & Stringer, S. P. (2011). Head and Neck Manifestations of Thalassemia. The Laryngoscope, 121(S4), S62-S62. Filon, D., Faerman, M., Smith, P., & Oppenheim, A. (1995). Sequence analysis reveals a β–thalassaemia mutation in the DNA of skeletal remains from the archeological site of Akhziv, Israel. Nature Genetics, 9(4), 365-368. Hamidi, Z. (2012). What We Learn from Bone Complications in Congenital Diseases? Thalassemia, an Example. INTECH Open Access Publisher. Ironhealthalliance.com, (2015). Epidemiology and Pathophysiology of Thalassemia | Iron Health Alliance. (2015). Retrieved from http://www.ironhealthalliance.com/disease-states/thalassemia/epidemiology-and-pathophysiology.jsp Lagia, A., Eliopoulos, C., & Manolis, S. (2007). Thalassemia: macroscopic and radiological study of a case. International Journal of Osteoarchaeology, 17(3), 269. Manzon, V. S. (2007). Β-THALASSEMIA: THE ANAEMIA COMING FROM THE SEA. Ortner, D. J. (2003). Identification of pathological conditions in human skeletal remains. Academic Press. Perisano, C., Marzetti, E., Spinelli, M., Callà, C., Graci, C., & Maccauro, G. (2012). Physiopathology of Bone Modifications in -Thalassemia. Anemia, 2012, 1-5. Read More