Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary hyperferritinaemia cataract syndrome (HHCS) is characterized by hyperferritinaemia without iron overload. It is essential to differentiate true iron accumulation from HHCS as these patients rapidly develop iron-deficient anaemia when subjected to phlebotomies. The diagnosis of HHCS relies on the identification of point mutations or deletions present in the iron-responsive element of the first exon of the L-ferritin gene. However, many samples referred for diagnosis of putative HHCS are normal. To avoid unnecessary DNA sequencing, we have developed a diagnosis strategy based on the screening of the target DNA region by denaturing gradient gel electrophoresis. This method enabled the accurate identification of 11 different previously known mutations. This strategy will be of interest for family studies or for the screening of large series of patients.
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PMID:Denaturing gradient gel electrophoresis screening for mutations in the hereditary hyperferritinaemia cataract syndrome. 1116 83

Hereditary hyperferritinemia-cataract syndrome is a genetic condition characterized by constitutively increased serum ferritin values in the absence of iron overload and by bilateral cataract. It has been demonstrated that mutations in the stem loop structure of the iron regulatory element (IRE) located in the 5'-untranslated region of the ferritin L-subunit gene (19q13.1) are responsible for the anomalous expression of this protein. Although not clearly explained, cataract formation seems secondary to the increased levels of ferritin in the lens. We analyzed a large Basque family in order to identify possible germline alterations of the iron regulatory element of the ferritin-L gene in affected individuals and first-degree relatives. All members of the family presented hyperferritinemia and cataract except a young child who had hyperferritinemia but did not present cataract. Sequence analysis permitted the identification of an A40-->G mutation in all members, including this child. This could demonstrate that cataract formation is a consequence of ferritin accumulation in the lens.
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PMID:Molecular analysis of hereditary hyperferritinemia-cataract syndrome in a large Basque family. 1130 47

Ferritin, the iron-storing molecule, is made by the assembly of various proportions of 2 different H and L subunits into a 24-mer protein shell. These heteropolymers have distinct physicochemical properties, owing to the ferroxidase activity of the H subunit, which is necessary for iron uptake by the ferritin molecule, and the ability of the L subunit to facilitate iron core formation inside the protein shell. It has previously been shown that H ferritin is indispensable for normal development, since inactivation of the H ferritin gene by homologous recombination in mice is lethal at an early stage during embryonic development. Here the phenotypic analysis of the mice heterozygous for the H ferritin gene (Fth(+/-) mice) is reported, and differences in gene regulation between the 2 subunits are shown. The heterozygous Fth(+/-) mice were healthy and fertile and did not present any apparent abnormalities. Although they had iron-overloaded spleens at the adult stage, this is identical to what is observed in normal Fth(+/+) mice. However, these heterozygous mice had slightly elevated tissue L ferritin content and 7- to 10-fold more L ferritin in the serum than normal mice, but their serum iron remained unchanged. H ferritin synthesis from the remaining allele was not up-regulated. This probably results from subtle changes in the intracellular labile iron pool, which would stimulate L ferritin but not H ferritin synthesis. These results raise the possibility that reduced H ferritin expression might be responsible for unexplained human cases of hyperferritinemia in the absence of iron overload where the hereditary hyperferritinemia-cataract syndrome has been excluded. (Blood. 2001;98:525-532)
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PMID:H ferritin knockout mice: a model of hyperferritinemia in the absence of iron overload. 1146 45

At the Hospital in Lund a new central building was opened in 1850 bringing the total number of beds up to 150. In the same year the hospital was divided into one "External" department including surgery and the maternity ward and one "Internal" including medicine and the ward for venereal diseases. We reviewed the patient charts and the yearly reports from 1851 to 1860 including 40 autopsy reports from this period. During these years, 8,785 patients were admitted, 2,292 of these for syphilis. Mean hospitalization time in the surgical department was 55-60 years, average 35-45 days, in the medical department a mean of around 45 days. The longest hospital stay was 350-900 days, mostly for patients with joint diseases, probably mainly tuberculosis. The number of patients admitted each year, the number of hospital days, age distribution of the patients and costs are presented in diagrams. The mean age of the patients was around 28 years, and the largest 5-year group was 16-20 years. Syphilis, various manifestations of tuberculosis and different kinds of diffuse gastric trouble were dominating diagnoses. Infectious diseases were common and serious during these years, but only very few patients, apart from the diagnoses mentioned above, were admitted to the hospital. Chlorosis, anaemia and rheumatic disorders were common. Hirudines, cupping, in some cases venesection or cauterization, locally irritating cataplasms, laxatives and enemas were dominating parts of the therapeutic resources. The operative activity was very moderate, only a total of 275 operations were performed for incarcerated hernia, stone, cataract, external tumour and injuries. Medical drugs were collected mostly from plants but various preparations of iron, mercury and lead and their salts were also frequently used. Quinine was the only drug for fevers, not only for malaria,. Several lay "bonesetters" were active in the area, the best known of whom, belonging to a family active for 200 years, were mentioned with some criticism in a few patient charts. Clinical education for the medical students was conducted by A.S. Bruzelius, director of the "Institutum Clinicum", and the professors of surgery and medicine had only limited access to inpatients for their teaching. In 1850, Bruzelius was relieved from the teaching of internal medicine, and this became the reason to divide the hospital into the two departments. The organization of medical education in Sweden was much discussed during most of last century after the Karolinska Institute in Stockholm was opened in 1812 as an addition to the universities in Uppsala and Lund. In 1859 a committee suggested that, since the number of patients available for the medical students in Uppsala and Lund (which we can verify for Lund) were very modest compared to the hospitals in Stockholm, all medical education should be concentrated to one medical school in Stockholm. Fortunately, it all ended with a compromise. Otherwise, the two universities might have been closed completely, since the faculties of medicine were very important parts of the universities of this time.
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PMID:[The hospital in Lund during the 1850's]. 1163 43

Hereditary hyperferritinaemia-cataract syndrome (HHCS) is an autosomal dominant disease caused by mutations in the iron responsive element (IRE) of the l-ferritin gene. Despite the elucidation of the genetic basis, the overall clinical spectrum of HHCS has been less well studied as, to date, only individual case reports have been described. Therefore, we studied a total of 62 patients in 14 unrelated families, with nine different mutations. No relevant symptoms other than visual impairment were found to be associated with the syndrome. A marked phenotypic variability was observed, particularly with regard to ocular involvement (i.e. age range at which cataract was diagnosed in 16 subjects with the C39T: 6-40 years). Similarly, serum ferritin levels varied substantially also within subjects sharing the same mutation (i.e. range for the A40G: 700-2412 microg/l). We followed an HHCS newborn in whom well-defined lens opacities were not detectable either at birth or at 1 year. The lens ferritin content was analysed in two subjects who underwent cataract surgery at different ages, with different cataract morphology. Values were similar and about 1500-fold higher than in controls. These observations suggest that: (i) in HHCS the cataract is not necessarily congenital; (ii) in addition to the IRE genotype, other genetic or environmental factors may modulate the phenotype, especially the severity of the cataract.
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PMID:Clinical, biochemical and molecular findings in a series of families with hereditary hyperferritinaemia-cataract syndrome. 1170 32

Superoxide radicals have been implicated in the pathogenesis of aging, cataract, ischemia-reperfusion, cancer and inflammatory diseases. In the present work, we found that deferiprone (L1), an iron-chelating drug, and dietary dihydroxycinnamic acids (catechols) were much more effective at protecting isolated rat hepatocytes against hypoxia-reoxygenation injury if complexed with Fe(3+). Furthermore, the 2:1 catechol-metal complexes with Cu(2+), Fe(2+), and Fe(3+) were also more effective than uncomplexed catechols in scavenging superoxide radicals generated enzymically (xanthine oxidase/hypoxanthine). The 2:1 deferiprone:Fe(3+) complex was less effective at scavenging enzymically generated superoxide radicals even though it was effective at preventing hepatocyte hypoxia-reoxygenation injury. On the other hand, the 1:1 deferoxamine:Fe(3+) complex, another iron-chelating drug, did not prevent hepatocyte hypoxia-reoxygenation injury and did not scavenge enzymically generated superoxide radicals. Furthermore, hepatocytes readily reduced the 2:1 deferiprone:Fe(3+) complex but not the deferoxamine:Fe(3+) complex. These results suggest that the initial step in superoxide radical scavenging (SRS) activity is the formation of a redox complex between Fe(3+) and deferiprone or catechols. The [deferiprone:Fe(3+)] complex was more cytoprotective than would be expected from its SRS activity. This suggests that [deferiprone:Fe(3+)] complex is reduced by a ferrireductase present on the hepatocyte membrane to form [deferiprone:Fe(2+)] complex, which then scavenges superoxide radicals. Therefore, the clinically used deferiprone (L1) may have therapeutic advantages over deferoxamine in having a double role therapeutically: (a) it chelates iron to alleviate iron overload pathology, and (b) the readily formed iron complex protects hepatocytes from superoxide radical-mediated hypoxia-reoxygenation injury.
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PMID:Iron complexes of deferiprone and dietary plant catechols as cytoprotective superoxide radical scavengers(1). 1175 10

Agricultural evaporation basins are used as a means to dispose of highly saline underground-tile-drainage water in the San Joaquin Valley (California, USA). The hypersaline water conditions encourage high aquatic invertebrate production, primarily brine shrimp (Artemia franciscana), which attract birds to these sites. Cool winter temperatures (< 4 C) and hypersaline water conditions (> 70,000 mumhos/cm) resulted in feather salt encrustation and salt toxicosis in ruddy ducks (Oxyura jamaicensis). During December 1998 and January 1999, approximately 200 dead and sick ruddy ducks were collected from an evaporation basin and five healthy control ruddy ducks were collected from a freshwater wetland. Brains contained > or = 1,890 ppm sodium (wet tissue mass) in seven dead birds and contained < or = 1,150 ppm sodium in the control birds. Liver arsenic, lead, and mercury concentrations were < 1 ppm in all birds examined. Manganese, molybdenum, and copper liver concentrations did not differ significantly (P > 0.05) between the two groups of ducks. The dead ducks had significantly higher liver selenium, cadmium, iron, and zinc than the controls, but the concentrations were not sufficient to cause toxicity. Significant gross and microscopic lesions in most of the dead birds included conjunctivitis, lens opacity and cataract formation, vascular congestion in various organs most notably in the meninges of the brain, and myocardial and skeletal muscle degeneration.
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PMID:Salt toxicosis in ruddy ducks that winter on an agricultural evaporation basin in California. 1183 3

In the last few years, mutations that cause disease through increased efficiency of mRNA translation have been discovered. Hereditary hyperferritinaemia-cataract syndrome (HHCS) arises from various point mutations or deletions within the iron-responsive element (IRE) in the 5'-UTR of the L-ferritin mRNA. Each unique mutation confers a characteristic degree of hyperferritinaemia and severity of cataract in affected individuals. We report a novel six-nucleotide deletion identified in an Italian family presenting with elevated serum ferritin and early onset bilateral cataract. This deletion involves a sequence with a TCT repetition and may have occurred through a mechanism of slippage mispairing. Because of the above repetition, the observed mutation can be interpreted as deletion 22-27, 23-28, 24-29 or 25-30. Structural modelling predicted an IRE stem modification that is expected to markedly reduce the binding to iron-regulatory proteins. A double-gradient denaturing gradient gel electrophoresis (DG-DGGE) method easily detected the above deletion.
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PMID:A novel deletion of the L-ferritin iron-responsive element responsible for severe hereditary hyperferritinaemia-cataract syndrome. 1184 30

Total antioxidant activity of the lacrimal fluid (TAALF) was studied by luminol-dependent iron-induced chemiluminescence in an original model system on citrate phosphate buffer. Total antioxidant activity was estimated in percent of control (light sum of the model system fluorescence). The mean decrease of the light sum of the model system fluorescence in the presence of normal human lacrimal fluid supernatant was more than 50%, in glaucoma 67.2 +/- 4.43%, in cataract 58.5 +/- 2.61%, and in uveitis 76.9 +/- 1.13% of control. Traditional therapy of uveitis was associated with an increase of TAALF. Use of the proposed method for TAALF evaluation together with clinical data allows justified and individual antioxidant treatment of patients with ocular diseases and helps monitor the treatment efficiency. The study is noninvasive, cheap, and simple, which recommends evaluation of TAALF in clinical practice as a rapid test indicating the level of free radical oxidation in ocular tissues.
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PMID:[Total antioxidant activity of the lacrimal fluid]. 1208 1

Hereditary hyperferritinaemia-cataract syndrome (HHCS) (OMIM #600886) is a rare autosomal dominant condition identified by high serum ferritin levels with normal iron saturation and distinctive bilateral cataract. It may be misdiagnosed as haemochromatosis and such patients become anaemic as a result of inappropriate venesection. The elevated serum ferritin is due to a mutation in the iron-responsive element (IRE) of the l-ferritin gene, resulting in excessive l-ferritin production. We report the identification of three Australian pedigrees; one with a previously described mutation at position 40, a pedigree with a novel mutation at position 39 and an individual with a de novo mutation at position 32 of the l-ferritin IRE.
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PMID:Mutation spectrum in Australian pedigrees with hereditary hyperferritinaemia-cataract syndrome reveals novel and de novo mutations. 1219 4


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