Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary ceruloplasmin deficiency with hemosiderosis (aceruloplasminemia) is a newly recognized autosomal recessive disorder of copper-iron metabolism due to mutations in the ceruloplasmin (Cp) gene. We report here a novel mutation in the Cp gene in a 54-year-old Japanese woman with this disease. She showed clinical triad; diabetes mellitus, retinal degeneration and neurological disorder in her middle age. Laboratory findings were characteristic for no detectable serum ceruloplasmin and increased serum ferritin. Liver biopsy revealed excessive storage of iron in hepatocytes and magnetic resonance imaging of the brain was indicative of increased iron content in the basal ganglia, thalamus and dentate nucleus. The a-->g substitution at the splice acceptor site of the intron 6 (1209-2) caused a 8-bp deletion in Cp mRNA by defective splicing, resulting in a premature termination codon at the amino acid position 388. Truncation of Cp, even if effectively translated, may cause loss of its normal function because of drastic change in its triangular structure.
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PMID:A novel splicing mutation in the ceruloplasmin gene responsible for hereditary ceruloplasmin deficiency with hemosiderosis. 955 83

With recent therapeutic advances, thalassemic patients can now reach adulthood and attain reproductive capacity. Endocrine complications due to hemosiderosis and especially hypogonatotropic hypogonadism, which present either with sexual infantilism and primary amenorrhea or with secondary amenorrhea, are common in thalassemic women. The aim of this study was to estimate the frequency of fertility among our female thalassemic patients. Our population included 50 married women with thalassemia major (TM) and 12 with thalassemia intermedia (TI) who are regularly followed in our thalassemic centers. Of the 50 patients with TM, 7 had primary amenorrhea (PA), 9 had secondary amenorrhea (SA), and 34 had normal menstrual function (NM), as did all the patients with TI. Overall we had 62 women who were able to achieve 90 pregnancies and give birth to 87 healthy babies. Most of our patients became pregnant around the age of 25 years. Associated endocrine complications were rare except in the group of patients with PA, as expected. In all patients with PA and SA, the 17 pregnancies were induced (intercourse 10, insemination 3, IVF 4). In the patients with NM and TI, 66 pregnancies were achieved spontaneously and 7 following induction (insemination 3, IVF 4). There were four twin and one triple pregnancies, which all resulted in premature deliveries. Among the seven couples in which both partners had thalassemia major, sperm donation was used in 5 cases, ovum donation in one case, and one pregnancy was achieved spontaneously. These 90 pregnancies resulted in 69 full-term, 12 pre-term, 7 abortions and 2 stillbirths. No severe obstetric complication was observed except for two patients with preeclampsia. One patient with PA who carried the triple pregnancy developed severe cardiac failure, which was successfully treated. Transfusion requirements were increased during pregnancy. Discontinuation of desferrioxamine resulted in elevation of ferritin levels during the second and third trimesters of pregnancy and after delivery. Nine patients who were examined with cardiac echo had a transient increase of ESD and EDD during pregnancy, with return to normal after delivery. Labor was performed by Caesarian section in 26 births (26%) out of the 81 successful pregnancies. These collected data represent the largest number of pregnancies in thalassemic females reported so far and are clearly encouraging for the ultimate improvement of the quality of life in thalassemic patients.
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PMID:Fertility in female patients with thalassemia. 1009 Nov 68

We report a 49-year-old female with hereditary ceruloplasmin deficiency with hemosiderosis. There was a family history of the same symptoms; her brother showed hypoceruloplasminemia and decrease of the serum copper content. On physical examinations, dementia, dysarthria, downbeat nystagmus, sensorineural hearing disturbance, orthostatic hypotension, retinitis pigmentosa, diffuse goiter, and cerebellar ataxia were noted. Laboratory examinations disclosed leukopenia, diabetes mellitus, hypothyroidism, decrease of copper content in the serum and urine. Serum ferritin concentration was remarkably increased. Serum ceruloplasmin could not be detected. Biopsy of the liver showed that iron content in the liver was increased. On MRI study, dentate nucleus of the cerebellum, basal ganglia, and the liver showed low intensity in both T1 and T2 weighted images. A nonsense mutation in the ceruloplasmin gene was found in this patient. Systemic iron deposition and tissue damage were considered as caused by deficiency of function of ceruloplasmin as ferroxidase. To our knowledge, the characteristic combination of the clinical signs in this patient has not been reported.
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PMID:[A case of hereditary ceruloplasmin deficiency with hemosiderosis]. 1039 Oct 79

Two weeks before dying of congestive heart failure, a juvenile black rhinoceros (Diceros bicornis minor) received a single low dose of doxorubicin as part of combination chemotherapy for acute lymphoblastic leukemia. Diffuse hemosiderosis was present at necropsy in a pattern indicative of dietary iron overload, but unique iron-positive degenerative lesions were found in isolated myocardiocytes. Serum analyses revealed hyperferremia, 87% transferrin saturation, and 5- to 10-fold elevations in ferritin concentration, reflecting markedly increased tissue iron stores. Since both toxic and therapeutic effects of anthracyclines are mediated by formation of reactive free radicals via iron-catalyzed reactions, these observations suggest that iron overload may have enhanced myocardial susceptibility to cardiotoxic effects of doxorubicin. Impairments in other myocardial antioxidant defenses, such as deficiencies in catalase and glutathione S-transferase that are known to exist in rhinoceros erythrocytes, may have been underlying factors contributing to an inherent sensitivity of rhinoceros tissues to oxidant-induced injury.
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PMID:Anthracycline cardiotoxicity in a black rhinoceros (Diceros bicornis): evidence for impaired antioxidant capacity compounded by iron overload. 1064 86

The exact differential diagnosis of iron overload syndromes is mandatory as important therapeutic consequences may derive from a correct diagnosis, especially when hemochromatosis is present. To facilitate diagnostic and therapeutic decisions algorithms and probabilistic calculations based on different frequencies of clinical symptoms and typical laboratory findings of the diseases in question have been proposed. Overestimation and/or underestimation of clinical symptoms and/or laboratory findings in using such calculations, however, may lead to incorrect diagnosis and therapy as demonstrated in this case. We report on a 62-year-old patient with arthralgia, pathologic glucose metabolism, brown skin pigmentation and excessively elevated ferritin and transferrin saturation levels, which initially were interpreted as signs of the assumed underlying disease (hemo-chromatosis) based on a high initial suspicion level and further corroborated by Bayesian probability analysis yielding a probability 99.0 % for the presence of hemochromatosis. Because of this high probability and the patient's wish for treatment phlebotomy was started, but stopped after having obtained negative results of genetic testing and normal quantitative liver iron values. The diagnosis of hemochromatosis had to be revised and symptoms and laboratory findings of this patient were found to be compatible with chronic fatty liver and pathologically altered iron metabolism due to chronic alcohol intake which the patient has initially concealed. The joint pain was explained in terms of chronic degenerative bone destruction, the impaired glucose tolerance seen as the consequence of obesity and the skin pigmentation was ascribed to sun exposure due to the patient's outdoor activities as a hobby farmer not evaluated during initial presentation. The implications and importance of unbiased history taking, critical interpretation of clinical symptoms and laboratory findings in using probabilistic calculations and diagnostic decision analysis are emphasized and the different mechanisms of iron metabolism in hemochromatosis and hemosiderosis are discussed.
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PMID:[Hemochromatosis or hemosiderosis? Initial misinterpretation of clinical symptoms and laboratory findings in a 62-year-old patient]. 1196 34

Excessive ineffective erythropoiesis in thalassemia intermedia may cause paravertebral pseudotumors of extramedullary hematopoiesis. Due to the proximity to the spinal canal, these paravertebral masses carry the risk of severe neurological damage. Treatment strategies include hypertransfusion, radiotherapy, and laminectomy. Hydroxyurea, stimulating fetal hemoglobin synthesis, may represent an alternative therapeutic approach. We report on a 26-year-old patient suffering from thalassemia intermedia with progressive anemia symptoms and presenting multiple intrathoracic paravertebral pseudotumors of extramedullary hematopoiesis. Hypertransfusion therapy and splenectomy were followed by regular transfusion (baseline hemoglobin 10 g/dl) and chelation with desferrioxamine. With this treatment, clinical symptoms disappeared, paravertebral hematopoietic masses did not progress, but severe hemosiderosis developed within a few years. Hydroxyurea therapy was initiated to increase the efficacy of erythropoiesis, thereby reducing the required transfusion volume but suppressing concomitantly further expansion of extramedullary hematopoiesis, and finally leading to a reduction of transfusional iron load. Treatment was started with 4 mg/kg per day and stepwise increased to 12.5 mg/kg per day. The fetal hemoglobin concentration increased from 4.5 to 5.5 g/dl after 1 year and to 9.9 g/dl after 2 years of treatment. The yearly transfusion volume was halved during the 1st year of treatment. At present, after 26 months of treatment, the patient has been transfusion-independent for 10 months. Serum ferritin levels decreased from 2844 to 1335 ng/ml. Size and shape of paravertebral hematopoietic pseudotumors remained stable. No side effects of hydroxyurea have been observed. In thalassemia intermedia patients with extramedullary hematopoiesis, hydroxyurea may lead to independence from regular transfusion therapy without further expansion of ectopic hematopoietic tissue.
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PMID:Treatment with hydroxyurea in thalassemia intermedia with paravertebral pseudotumors of extramedullary hematopoiesis. 1222 8

Hemosiderin deposits in rats and in man were studied and compared by means of electron and light microscopy. Typical, isotropic, iron-positive hemosiderin granules were found to contain innumerable, closely packed, electron-dense particles, embedded in matter that was much less dense to electrons. Similar dense particles were often scattered diffusely through the cytoplasmic matrix of cells containing hemosiderin granules. In cells of proximal convoluted tubules of rats given repeated intraperitoneal injections of hemoglobin the hemosiderin granules contained dense particles with a mean diameter of 55 A, and with a size-frequency distribution that indicated uniformity. These particles corresponded in size to the iron micelles of ferritin molecules. There was less uniformity of particles in hemosiderin granules situated in liver and reticulo-endothelial cells of rats that had been given a diet containing ethionine. The dense aggregates representing hemosiderin granules were often situated inside discrete cytoplasmic organelles that were bordered by membranes, and sometimes contained "cristae"; and often the membranous borders were markedly disrupted. The term "sidersomes" is proposed for these specialized cytoplasmic structures which may be derivatives of mitochondria, and apparently play a part in the formation of hemosiderin. Ferritin was crystallized from the livers and kidneys of the hemosiderotic rats with ease, but could not be crystallized from comparable quantities of liver and kidney tissue of untreated control rats. Specimens from the liver and spleen of a patient with advanced hemosiderosis, obtained at an operation, were also studied. In liver and reticulo-endothelial cells many particles with diameters of about 60 A were scattered through the cytoplasmic matrix. By contrast, hemosiderin granules in the same cells contained particles that varied considerably in size. In representative granules, examined at high resolution, the size-frequency distribution of particle diameters displayed a periodicity consistent with the presence of small, uniform subunits. Electron micrographs of ferritin, isolated from the spleen of the same patient, provided confirmation for the inferences that the dense particles observed inside cells are iron micelles, and that ferritin is probably a component of hemosiderin.
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PMID:A study of hemosiderosis with the aid of electron microscopy; with observations on the relationship between hemosiderin and ferritin. 1344 32

Injections of hemoglobin were given to rats in order to produce hemosiderosis, and selected hemosiderin granules in sectioned cells of proximal convoluted tubules were studied by means of electron microscopy. When examined at high resolution, many of the dense particles that were present in hemosiderin granules proved to have the structure that characterizes the iron hydroxide micelles of molecular ferritin. In some hemosiderin deposits the dense particles formed lattices similar to those present in sections of crystalline ferritin. Such ordered arrangement of dense particles was encountered inside as well as outside of the cytoplasmic organelles for which the name "siderosomes" has been proposed previously, and which may be derived from mitochondria. Study of hemosiderin granules in hepatic parenchymal and reticuloendothelial cells of human beings yielded similar results. The findings confirm the inference that ferritin is a component of hemosiderin, and they indicate that some of the so called hemosiderin granules are crystals of ferritin.
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PMID:Electron microscopy of hemosiderin; presence of ferritin and occurrence of crystalline lattices in hemosiderin deposits. 1350 28

Using three different methods of cells fractionation, hemosiderin granules were isolated from tissues (liver and/or spleen) of three patients. The samples were obtained from a case of idiopathic hemochromatosis, a case of thalassemia major with secondary (transfusional?) hemosiderosis, and a case of transfusional hemosiderosis associated with an unclassified anemia. Iron, nitrogen, and protein content of the hemosiderin granules varied over a wide range. Electron microscopy of sectioned granules revealed aggregates of dense particles of different shapes, with diameters ranging from 10 A to about 75 A. In some of the granules dense particles corresponding to the iron hydroxide micelles of ferritin molecules were abundant. But many of the granules contained very few of these molecules. The presence of ferritin and apoferritin in the samples of hemosiderin granules was demonstrated by means of precipitin tests in agar-gel, using rabbit antiferritin sera with known antibody nitrogen concentrations. At least three antigenic components were detected in highly purified crystalline ferritin prepared from tissues of the three patients; the hemosiderin granules contained the same antigens, but probably in much smaller quantities. Both ferritin and apoferritin molecules were extracted from hemosiderin granules, and were demonstrated in the electron microscope after suitable preparation. The solubility curve of human ferritin in solutions of (NH(4))(2)SO(4) was investigated. The results indicate that substantial quantities of ferritin or apoferritin can be lost in saline, aqueous media during isolation of hemosiderin granules from cells. It was shown by means of electron microdiffraction on selected hemosiderin granules that the dense particles represent forms of partly hydrated alpha-Fe(2)O(3). The conditions necessary for electron microdiffraction in an electron microscope precluded an exact determination of the state of hydration of the alpha-Fe(2)O(3) or of its structural relation to (FeOOH) micelles of pure ferritin in its undenatured state. The findings were considered in the light of evidence on the structure and disposition of hemosiderin in situ in cells, and on the structure of ferritin. Differences between endogenous hemosiderin and hemosiderin derived from injections of colloidal iron compounds were pointed out. The evidence indicates that in hemochromatosis and in secondary hemosiderosis much of the inorganic storage iron in liver and spleen is derived from degraded ferritin. The findings suggest that an abnormal cellular metabolic pathway of ferritin is implicated in the pathogenesis of hemochromatosis and transfusional hemosiderosis.
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PMID:The nature of storage iron in idiopathic hemochromatosis and in hemosiderosis. Electron optical, chemical, and serologic studies on isolated hemosiderin granules. 1374 89

Hepatic hemosiderosis and increased iron absorption are common findings in cirrhosis. It has been proposed that a positive relation exists between intestinal iron absorption and the development of hepatic hemosiderosis. The current study investigated the duodenal expression of the iron transport molecules divalent metal transporter 1 (DMT1 [IRE]), iron-regulated gene 1 (Ireg1 [ferroportin]), hephaestin, and duodenal cytochrome b (Dyctb) in 46 patients with cirrhosis and 20 control subjects. Total RNA samples were extracted from duodenal biopsy samples and the expression of the iron transport genes was assessed by ribonuclease protection assays. Expression of DMT1 and Ireg1 was increased 1.5 to 3-fold in subjects with cirrhosis compared with iron-replete control subjects. The presence of cirrhosis per se and serum ferritin (SF) concentration were independent factors that influenced the expression of DMT1. However, only SF concentration was independently associated with Ireg1 expression. In cirrhosis, the expression of DMT1 and Ireg1 was not related to the severity of liver disease or cirrhosis type. There was no correlation between the duodenal expression of DMT1 and Ireg1 and the degree of hepatic siderosis. In conclusion, the presence of cirrhosis is an independent factor associated with increased expression of DMT1 but not Ireg1. The mechanism by which cirrhosis mediates this change in DMT1 expression has yet to be determined. Increased expression of DMT1 may play an important role in the pathogenesis of cirrhosis-associated hepatic iron overload.
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PMID:Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis. 1476 3


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