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)

Hemochromatosis is an autosomal recessive genetic disorder that occurs with high prevalence in populations of European origin. The gene that is abnormal in hemochromatosis is found on the short arm of chromosome 6 in close proximity (approximately 1 centimorgan) to HLA-A, but the product coded for by that gene is unknown. The pathogenetic mechanism in hemochromatosis is that of continued, excessive absorption of dietary iron with loss of normal control mechanisms, leading to a gradual but vast expansion of storage iron as ferritin and especially as hemosiderin. Through mechanisms that probably include peroxidation of lipid membranes, the excess iron injures hepatocytes, islet B cells, gonadotropes in the anterior pituitary, myocardium, synovial cells, and chondrocytes, and probably other cells and tissues as well. Most patients with hemochromatosis remain undiagnosed throughout life. Removal of the excess iron by phlebotomy will prevent all of the complications of hemochromatosis when begun early and will significantly improve survival in virtually all patients. It is important, therefore, that the diagnosis of hemochromatosis be considered much more frequently in clinical medicine in order that this effective therapy be utilized.
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PMID:Overview of hemochromatosis. 221 95

Primary hemochromatosis is a genetic disorder rarely recognized in childhood; its long-term consequences include cirrhosis and liver cancer. We report a family with primary hemochromatosis affecting three generations, including a 7-year-old child and a 29-month-old child; these are the youngest children with primary hemochromatosis yet reported. The pathophysiology, genetics, and clinical findings of this disorder are reviewed. Serum ferritin and transferrin saturation are useful screening tests; definitive diagnosis, however, depends on determination of hepatic iron content. A plan for evaluating and treating affected patients is proposed. Physicians caring for children must learn to recognize this potentially treatable disorder.
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PMID:Primary hemochromatosis in childhood. 365 74

Recently, we described a new genetic disorder (the "hereditary hyperferritinemia-cataract syndrome") clinically characterized by the combination of elevated serum ferritin and congenital bilateral nuclear cataract, both cotransmitted as an autosomal dominant trait. In affected subjects, hyperferritinemia (ranging from 950 to 2,259 micrograms/L) is typically not related to iron overload. Differently from subjects with hereditary hemochromatosis, they have normal to low levels of serum iron and percent of transferrin saturation and absence of iron overload in parenchymal organs. When unnecessary phlebotomies are performed, they rapidly develop iron-deficient anemia, with persistently elevated levels of serum ferritin. By RNA-single-strand conformation polymorphism screening of the L-subunit ferritin gene on chromosome 19, we were able to identify in affected subjects a mutation in the 5' untranslated region. This mutation involves the five nucleotides sequence [CAGUG] of the iron-responsive element (IRE), which is critical for the posttranscriptional regulation of ferritin synthesis by means of IRE-binding protein (IRE-BP). Thus, it is very likely to provide the molecular basis for the iron-insensitive upregulation of ferritin synthesis in affected subjects.
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PMID:Molecular basis for the recently described hereditary hyperferritinemia-cataract syndrome: a mutation in the iron-responsive element of ferritin L-subunit gene (the "Verona mutation") 878 50

The only genetic disorder with elevated serum ferritin levels so far described is hereditary HLA-related haemochromatosis. On the other hand, hereditary cataract is both genotypically as well as phenotypically heterogenous, and no specific locus or any useful marker has been yet identified. We studied two Italian families in whom a combination of elevated serum ferritin not related to iron overload and congenital nuclear cataract is transmitted as an autosomal dominant trait. Affected individuals have normal serum iron and transferrin saturation, but high serum ferritin. Red cell counts are normal and venesection therapy rapidly produces iron-deficiency anaemia. This genetic disorder, which is characterized by hyperferritinaemia, differs from hereditary HLA-related haemochromatosis mostly for the absence of iron overload. A gene responsible for the congenital nuclear cataract likely maps on chromosome 19q close to the ferritin L-subunit gene. Within families with autosomal dominant congenital cataract, serum ferritin might be an early marker of disease.
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PMID:A linkage between hereditary hyperferritinaemia not related to iron overload and autosomal dominant congenital cataract. 766 75

Thalassemia is a common genetic disorder among the South Chinese. To see if thalassemia would adversely affect the erythrocyte response to recombinant human erythropoietin (rHuEPO, Epogen) in dialysis patients, the response to rHuEPO in 4 dialysis patients with thalassemic traits (thal-t) was compared with that of 4 control patients who were matched for age, sex, mode of dialysis and baseline hemoglobin levels over a 6-month period. Patients with thal-t showed a reduced erythrocyte response to rHuEPO compared to control dialysis patients as reflected by a reduced reticulocyte index, a slower rise in hemoglobin or hematocrit levels, requirement of a higher cumulated dose of rHuEPO to achieve a target hemoglobin of 10 g/dl and a higher maintenance dose of rHuEPO. A dialysis patient with hemoglobin H disease (HbHD) was also studied. He failed to respond to rHuEPO despite that the dose was increased to 250 U/kg/week. In contrast, his matched control dialysis patient, despite a lower baseline hemoglobin level (6.1 versus 8.8 g/dl), was able to reach a target hemoglobin level of 10 g/dl by 6 weeks and could be maintained at this level with 50 U/kg/week. The patient with HbHD had splenomegaly and a higher baseline serum erythropoietin level, reticulocyte count, serum bilirubin, serum ferritin and serum iron saturation than control patients and patients with thal-t. It was concluded that thal-t reduces the erythrocyte response to rHuEPO in dialysis patients and that in the presence of active hemolysis and enhanced endogenous erythropoietin secretion, dialysis patients with HbHD are resistant to treatment with rHuEPO.
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PMID:Influence of thalassemia on the response to recombinant human erythropoietin in dialysis patients. 834 81

Hereditary hemochromatosis (HHC) is an inherited disease transmitted in an autosomal recessive pattern. With homozygosity occurring in up to 0.5% of the population, HHC is the most prevalent genetic disease among the white population worldwide and has the same prevalence as the sickle cell trait in the African-American population. An asymptomatic 50-year-old white man presented at the family practice clinic and stated that HHC had been diagnosed in his mother. Laboratory findings showed markedly elevated transferrin saturation and ferritin levels. The diagnosis of HHC was made on the basis of the laboratory results and family history, and therapy was begun. Clinical manifestations of HHC occur late and include diabetes mellitus, cirrhosis, and cardiomyopathy. As end-organ damage is preventable, optimal management involves early diagnosis and lifelong phlebotomy. Diagnosis is made by an elevated transferrin saturation level and an increased serum ferritin value. Hereditary hemochromatosis is a genetic disorder of iron metabolism that has an excellent prognosis if diagnosed early.
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PMID:Hereditary hemochromatosis. 907 Dec 52

Recent reports have described families in whom a combination of elevated serum ferritin not related to iron overload and congenital nuclear cataract is transmitted as an autosomal dominant trait. We have studied the molecular pathogenesis of hyperferritinemia in two families showing different phenotypic expression of this new genetic disorder. Serum ferritin levels ranged from 950 to 1,890 microg/L in affected individuals from family 1, and from 366 to 635 microg/L in those from family 2. Cataract was clinically manifested in family 1 and asymptomatic in family 2. By using monoclonal antibodies specific for the H and L ferritin subunits, serum ferritin was found to be essentially L type in both normal and affected individuals. The latter also showed normal amounts of H-type ferritin in circulating mononuclear cells; on the contrary, L-type ferritin contents were 13 times normal in family 1 and five times normal in family 2 on average. Serum ferritin was glycosylated in both normal and affected individuals. There was a close relationship between mononuclear cell L-type ferritin content and serum ferritin concentration (r = 0.95, P < .00001), suggesting that the excess production of ferritin in cells was directly responsible for the hyperferritinemia. The dysregulated L-subunit synthesis was found to result from different point mutations in a noncoding sequence of genomic L-subunit DNA, which behaves as an mRNA cis-acting element known as iron regulatory element (IRE). Affected individuals from family 1 were heterozygous for a point mutation (a single G to A change) in the highly conserved, three-nucleotide motif forming the IRE bulge. Affected members from family 2 were heterozygous for a double point mutation in the IRE lower stem. Using a gel retardation assay, the observed molecular lesions were shown to variably reduce the IRE affinity for an iron regulatory protein (IRP), which inhibits ferritin mRNA translation. The direct relationship between the degree of hyperferritinemia and severity of cataract suggests that this latter is the consequence of excessive ferritin production within the lens fibers. These findings provide strong evidence that serum ferritin is a byproduct of intracellular ferritin synthesis and that the L-subunit gene on chromosome 19 is the source of glycosylated serum ferritin. From a practical standpoint, this new genetic disorder should be taken into account by clinicians when facing a high serum ferritin in an apparently healthy person.
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PMID:Hereditary hyperferritinemia-cataract syndrome: relationship between phenotypes and specific mutations in the iron-responsive element of ferritin light-chain mRNA. 1038 91

Iron availability regulates ferritin synthesis posttranscriptionally by the interaction between iron-regulatory proteins (IRPs) and an iron responsive element (IRE), a stem-loop sequence located on the 5' untranslated region of ferritin mRNA. IRPs recognize IREs as a sequence/structure motif, blocking ferritin translation. Recently, we and others independently described families with a combination of hyperferritinemia (serum L-ferritin > or = 1,000 microg/L, without iron overload) and congenital bilateral cataract, transmitted as an autosomal-dominant trait. The molecular basis were two distinct point mutations in the highly conserved CAGUG(X) hexaloop of L-ferritin IRE on chromosome 19. A new three-generation family with a similar phenotype and a unique genotype is here reported. DNA amplification by polymerase chain reaction and sequence analysis showed a 29-base pair deletion in the L-ferritin IRE, involving the whole 5' sequence essential to the base pairing of the IRE stem. This deletion is predicted to cause the disruption of IRE stem-loop secondary structure and the nearly complete abolition of the negative control of ferritin synthesis by IRE/IRP binding. Hereditary Hyperferritinemia-Cataract Syndrome (HHCS) appears as a new genetic disorder with a unique phenotype associated with at least four different mutations in the L-ferritin IRE. Hematologists should take into account HHCS in the differential diagnosis of unexplained hyperferritinemia.
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PMID:Hereditary hyperferritinemia-cataract syndrome caused by a 29-base pair deletion in the iron responsive element of ferritin L-subunit gene. 929 47

A new autosomal-dominant genetic disorder, which has been recently identified by our group is described. The disease is clinically characterized by the combination of a substantial increase of serum ferritin and early-onset bilateral cataract. Moreover, it is clearly distinguishable from genetic hemochromatosis because of: 1) normal to low serum iron and transferrin saturation, without evidence of parenchymal iron overload; 2) the dominant transmission; 3) the lack of any relation with HLA; 4) the rapid development of iron-deficient anemia when unnecessary phlebotomies are performed. The molecular basis of the new syndrome is a mutation in the L-subunit ferritin gene on chromosome 19 (19q13.3-->19qter). The mutation involves a five nucleotide sequence [CAGUG] of the iron-responsive-element (IRE), which is critical for the post-transcriptional regulation of ferritin synthesis by means of the binding with an Iron Regulatory Protein. As a consequence, ferritin synthesis is up-regulated, irrespective of cell iron status.
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PMID:["Hyperferritinemia-cataract syndrome." Description of a new hereditary disease, from anamnesis to molecular diagnosis]. 941 35

Haemochromatosis is a common autosomal recessive genetic disorder of iron metabolism. A candidate gene was recently identified (HLA-H) and two amino acid substitutions (C282Y and H63D) were characterized. Haemochromatosis probands (n = 478) from Brittany were selected from their iron status markers, primarily serum iron, serum ferritin and transferrin saturation. We investigated the relationships between haemochromatosis phenotype and genotypes at the HLA-H locus and surrounding markers. As already reported, we observed that the C282Y substitution is unambiguously associated with the haemochromatosis phenotype, haemochromatosis patients homozygous for the substitution (Tyr/Tyr) accounting for 81.2% of all haemochromatosis patients. A clear heterogeneity in serum ferritin and transferrin saturation values, and in iron removed by phlebotomy was observed among haemochromatosis patients that is correlated with the presence of two subgroups of individuals homozygous and non-homozygous for the mutant allele C282Y, the latter being characterized by lower phenotypic values. In this subgroup, sequencing did not reveal any other mutation in the HLA-H gene, hence the genotype remained unclear. Thus, an additional non-genetic cause, other mutations or another gene can not be excluded as explanations for the results in these patients.
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PMID:Phenotype-genotype correlation in haemochromatosis subjects. 943 54


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