Iron-storage disorders

Bacon BR, Britton RS Hemochromatosis and other iron storage disorders, in Schiff ER, Sorrell MF, MaddreyWC,et al. (eds) Schiff s Diseases of the Liver. Philadelphia, Lippincott Williams and Wilkins, 2003, pp. 1187-1205. 

In hemochromatosis a deferoxamine and penicillamine loading test has been tried in a few patients as diagnostic tool. Urinary iron excretion is increased in iron storage disorders after deferoxamine. 

Friedreich s ataxia is caused by an intronic triplet repeat expansion. Friedreich s ataxia is an autosomal recessive disorder characterized by progressive ataxia, nystagmus, distal sensory polyneuropathy and corticospinal tract degeneration. It is caused by an unstable expanded GAA repeat in intron 1 of the frataxin gene on chromosome 9ql3. This diminishes expression of frataxin, a mitochondrial iron-storage protein that participates in free radical metabolism [71]. 

De Domenico I, McVey Ward D, Kaplan J Regulation of iron acquisition and storage Consequences for iron-linked disorders. Nat Rev Mol Cell Biol 2008 9 72. 

Lysosomes are in effect a cellular waste-bin, and play an important role in the turnover and degradation of cytoplasmic organelles and phago-cytosed particles. They facilitate receptor-mediated endocytosis of many macromolecules from the cell membrane. Lysosomes carry hydrolases that degrade nucleotides, proteins, lipids and phospholipids they also remove carbohydrate, sulphate, or phosphate groups from molecules. Lysosomes store iron, either as soluble ferritin or as products of ferritin degradation, such as haemosiderin. Abnormalities associated with lysosomal function cause a variety of storage disorders such as Tay-Sachs disease [9]. 

The most common cause of iron overload is thalassemia, particularly in the parts of the world where it is prevalent (see earlier section). Indeed, the cardiac complications of iron overload are among the most common causes of death in I-thalassemia major. Sideroblastic anemias are a group of iron-loading disorders, many of which are of unknown cause. In a hereditary type of this disorder, there is deficiency of erythroid specific 5-aminolevulinic acid synthetase in RBC precursors because of mutations involving the X-linked gene that encodes this enzyme. Iron storage is common in patients with congenital dyserythropoietic anemia and may be found in patients with red cell enzyme deficiencies, particularly pyruvate kinase deficiency. ... 

Fairbanks VF, Brandhagen DJ. Disorders of iron storage and transport. In Beuder E, Lichtman MA, Coder BS, Kipps TJ, Seligsohn U, eds. Williams Hematology. New York McGraw-Hill, 2001 ... 

Skin In a prospective study in 78 patients with P-thalassemia aged 10 months to 37 years, skin disorders of any kind were observed in 65 (83%) pruritus and xerosis were the most common (Table 1) [3 ]. Adverse events can occur simultaneously xerosis, for example, was often associated with pruritus. Systemic medication was common in these patients 40 received deferoxamine by slow infusion over 8-12 hours, 5-7 days a week 25 received deferi-prone and 10 received deferasirox. Subcutaneous infusion of deferoxamine is a frequent cause of local reactions, reflected in this series by the occurrence of skin erythema or irritation in 10 patients. Xerosis was less common in those who received deferasirox than in those who received deferoxamine or deferiprone. Xerosis can occur because of iron storage and also in zinc deficiency. The high spontaneous prevalence of a variety of skin disorders in patients with p-thalassemia, as noted in this study, is of interest in the context of attributing skin events to the use of chelating agents. 

Iron imbalance, like Inflammation, has been recognized genetically in the etiology of neurological disorders. Consistent with these observations, the acute phase protein, alpha-1 antichymotrypsin [32] is associated with amyloid plaques and the iron storage protein ferritin is present in neuritic plaques [33,34]. 

Hereditary (primary) hemochromatosis is a very prevalent autosomal recessive disorder in certain parts of the world (eg, Scodand, Ireland, and North America). It is characterized by excessive storage of iron in tissues, leading to tissue damage. Total body iron ranges between 2.5 g and 3.5 g in normal adults in primary hemochromatosis it usually exceeds 15 g. The accumulated iron... 

Metabolic disorders such as Wilson s disease (copper storage disease) and haemochro-matosis (iron overload disease),... 

Anemia can be induced in animals on a low copper diet, such as milk, and appears 10 be due to an impaired ability of the body to absorb iron. This anemia, however, is rare, because of the widespread occurence of copper in foods. In locations, such as Australia and lire Netherlands, diseases of cattle and sheep, involving diarrhea, anemia and nervous disorders, can be traced either to a lack of copper in the diet, or to excessive amounts of molybdenum, which inhibits the storage of copper in the liver. 

Important disorders associated with transition metals include insufficient intake or absorption (e.g. iron deficiency anaemia), defective transport (e.g. Menkes syndrome), and excessive storage (e.g. Wilson s disease, haemochromatosis). 

Iron-platinum alloy nanoparticles are very promising candidates for future data storage systems. They become available by simultaneous reduction of platinum acetylacetonate and the decomposition of Fe(CO)5 in oleic acid and oleyl amine.The composition of FexPti x can be varied between X = 0.48 and x = 0.7. The particles exhibit disordered fee structure. They are superparamagnetic at room temperature. Aimealing at 550-600 °C transforms the fee structure into a face-centered tetragonal (fet) one. These have been shown to be suited for storage devices owing to their room temperature coercivity. The exact transition temperature depends on the stoichiometry. 

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