Sunday, June 14, 2009

Blood disorders

What is hemosiderosis?

Most iron is stored in the liver, lymph and skeletal muscles by use of a protein, ferritin (1). Ferritin consists of an apoprotein called apoferritin that is made up of H and L subunits (amino acids) synthesized dependent on concentration of free intracellular iron (1). Each protein can hold up from 3000 to 4500 iron atoms (1). When overload exceeds storage capacity, however, a partially degraded form of ferritin in spheres occurs called hemosiderin (1p252, 2p825). An accumulation of iron deposits via hemosiderin results in hemosiderosis (3).

What causes hemosiderosis?

Hemosiderosis can be inherited by way of a genetic mutation such as Bantu siderosis or Ferroportin disease. Previously thought to occur due to drinking too much beer, Bantu siderosis affects up to 10 percent of rural Africans and is associated with cirrhosis, heart disease and diabetes (4). Ferroportin disease is the most common genetic hemosiderosis and caused by gene mutation that disrupts ferroportin production (4).

Pulmonary hemosiderosis occurs due to over-accumulation of iron in the lung tissue (4). It can be a result of cardiovascular disease or a systemic disorder that mostly affects children (5). Anemia, lung scarring and coughing up blood are all symptoms (4). Corticosteroid therapy has been successful as a treatment and iron therapy or transfusion is important (5;6).

Renal hemosiderosis, hepatic hemosiderosis or other organ-specific hemosiderosis may occur due to hemolysis, leaving iron from hemoglobin to collect in the organs (4). Its cause can genetic or by an agent of some kind, which can lead to hepatocyte distruction and liver disease (5-8).

Transfusional hemosiderosis happens when a blood transfusion meant to treat anemia causes iron overload (4). Chelation therapy to extract iron is used to correct the problem (5;9).

What is Hb-C disorder?

Hemoglobin C disorder is a genetic missense mutation of hemoglobin resulting in a GAA or GAG codon for glutamate replaced with an AAA or AAG codon for lysine in the sixth position of a beta-globin (1p206). It is the most common hemoglobinopathy after sickle cell disorder (1p206).

What is pernicious anemia?

Pernicious anemia is not specifically an anemia, but a gastric disorder that can lead to megaloblastic anemia as well as neurological deterioration via demyelination of nervous tissue (1p1109, 2p483). The disorder was fatal until liver extracts were found in 1926 to be a cure (1p1109).

What is the cause of pernicious anemia?

The cause of pernicious anemia is lack of gastric intrinsic factor, which is required to absorb extrinsic factor cobalamin (vitamin B12), or a dietary deficiency of extrinsic factor cobalamin (1p1109, 2p483). Cobalamin is required for two enzymes in the body: methionine synthase, which drives homocysteine methylation to methionine, and methylmalmalonyl-CoA mutase, which drives conversion of methylmalonyl CoA to succinyl CoA (1p1109). Without cobalamin homocysteine and methylmalonic acid both accumulate causing the megaloblastic anemia (1p1109). The demyelination may be caused because methylmalonic acid inhibits and acts as a substitute for malonyl CoA in fatty acid biosynthesis (1p1110).

Reference List

1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
2. Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ. Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins, 2009.
3. Andrews GA, Chavey PS, Crawford G. Enzyme-linked immunosorbent assay to quantitate serum ferritin in black and white ruffed lemurs (Varecia variegata variegata). J Zoo Wildl Med 2005;36:648-52.
4. Aboutblooddisorders.com. Hemosiderosis and iron overload. Available at: http://www.about-blood-disorders.com/articles/iron-disorders/hemosiderosis.php. Accessed on 14 June 2009.
5. Deniz O, Onguru O, Ors F et al. Idiopathic pulmonary hemosiderosis in an adult patient responded well to corticosteroid therapy. Tuberk Toraks 2007;55:77-82.
6. YETTRA M, GOLDENBERG E, WEINER H. Idiopathic pulmonary hemosiderosis. Calif Med 1960;93:330-6.
7. Bale PM, Kan AE, Dorney SF. Renal proximal tubular dysgenesis associated with severe neonatal hemosiderotic liver disease. Pediatr Pathol 1994;14:479-89.
8. Carthew P, Dorman BM, Edwards RE, Francis JE, Smith AG. A unique rodent model for both the cardiotoxic and hepatotoxic effects of prolonged iron overload. Lab Invest 1993;69:217-22.
9. Giardina PJ, Grady RW. Chelation therapy in beta-thalassemia: the benefits and limitations of desferrioxamine. Semin Hematol 1995;32:304-12.