Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The term hemochromatosis is commonly used as synonymous with HFE-associated genetic iron overload but several rarer causes of an identical clinicopathological syndrome have been described in recent years. The most common symptoms are lethargy and arthralgia, and the major complications of end-stage disease are cirrhosis, diabetes, and cardiac and endocrine manifestations. However, with the development of cascade screening for family members of affected probands as well as screening for common diseases at health checks, hemochromatosis is being detected at increasingly early stages, often when there are only biochemical abnormalities. The available evidence from screening studies strongly suggests that approximately 75% of C282Y homozygous subjects have biochemical expression. Hepatic iron overload is present in approximately 56% and 34% of men and women, respectively, advanced hepatic fibrosis in 18.7% and 5.4%, respectively, and cirrhosis in 5.8% and 1.9%, respectively. In subjects with severe expression of the disease, additional modifying genetic mutations have been described including those in hepcidin and hemojuvelin. Treatment is by regular phlebotomy which, if instituted before the development of cirrhosis, results in normal life expectancy.
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PMID:Clinical aspects of hemochromatosis. 1631 32

A 14-year-old boy who presented with debilitating lethargy was shown to have an elevated serum ferritin of 572 microg/L and a C282Y homozygous HFE genotype. Liver iron concentration was measured non-invasively by magnetic resonance imaging, which revealed a liver iron concentration of 59 micromol/g dry weight (children's reference range < 14). The early phenotypic expression was further investigated by screening genomic DNA for the presence of co-inherited mutations in genes responsible for non-HFE haemochromatosis. Coding regions and splice sites in genes encoding hepcidin and haemojuvelin were sequenced and previously described mutations in ferroportin 1 and transferrin receptor 2 genes were screened. Although no mutations were found, the most likely cause for the early expression is the presence of novel mutations or gene(s).
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PMID:Clinical expression of C282Y homozygous HFE haemochromatosis at 14 years of age. 1670 63

A 30-year-old woman was found to have hyperferritinaemia after presenting with menorrhagia and lethargy. Serum iron studies did not confirm iron overload. Further investigations revealed two distinct genetic mutations of iron haemostasis--homozygosity for C282Y mutation of the HFE gene on chromosome 6 and heterozygosity for A40G mutation in the iron response element of ferritin light chain on chromosome 19. These mutations are responsible for the diseases hereditary haemochromatosis (autosomal recessive) and hereditary hyperferritinaemia-cataract syndrome (autosomal dominant) respectively. This is the first description of such a patient.
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PMID:Dual diagnoses of hereditary hyperferritinaemia-cataract syndrome and hereditary haemochromatosis. 1699 31

Hereditary hemochromatosis is an autosomal recessive disorder that disrupts the body's regulation of iron. It is the most common genetic disease in whites. Men have a 24-fold increased rate of iron-overload disease compared with women. Persons who are homozygous for the HFE gene mutation C282Y comprise 85 to 90 percent of phenotypically affected persons. End-organ damage or clinical manifestations of hereditary hemochromatosis occur in approximately 10 percent of persons homozygous for C282Y. Symptoms of hereditary hemochromatosis are nonspecific and typically absent in the early stages. If present, symptoms may include weakness, lethargy, arthralgias, and impotence. Later manifestations include arthralgias, osteoporosis, cirrhosis, hepatocellular cancer, cardiomyopathy, dysrhythmia, diabetes mellitus, and hypogonadism. Diagnosis requires confirmation of increased serum ferritin levels and transferrin saturation, with or without symptoms. Subtyping is based on genotypic expression. Serum ferritin measurement is the most useful prognostic indicator of disease severity. Liver biopsy is performed to stage the degree of fibrosis with severe ferritin elevation or transaminitis, or to diagnose nonclassical hereditary hemochromatosis in patients with other genetic defects. Treatment of hereditary hemochromatosis requires phlebotomy, and the frequency is guided by serial measurements of serum ferritin levels and transferrin saturation. Iron avidity can result from overtreatment. If iron avidity is not suspected, it may mimic undertreatment with persistently elevated transferrin saturation. Dietary modification is generally unnecessary. Universal screening for hereditary hemochromatosis is not recommended, but testing should be performed in first-degree relatives of patients with classical HFE-related hemochromatosis, those with evidence of active liver disease, and patients with abnormal iron study results. Screening for hepatocellular carcinoma is reserved for those with hereditary hemochromatosis and cirrhosis.
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PMID:Hereditary hemochromatosis. 2341 62

This review focuses on iron metabolism, the genetics of hemochromatosis, current treatment protocols and various screening methods. Even though the most common form of hereditary hemochromatosis, C282Y gene mutations in the HFE gene, has been extensively studied, novel mutations in both HFE and non-HFE genes have been implicated in this disease. These have important implications for the Asia-Pacific region. In overload, deposition of iron in various body tissues leads to toxic damage. Patients commonly present with non-specific symptoms of malaise and lethargy. Biochemical, imaging and genetic testing can be carried out to confirm diagnosis. Venesection forms the mainstay of treatment and at present cascade screening of affected families is recommended over population-level screening.
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PMID:Recent advances in hemochromatosis: a 2015 update : a summary of proceedings of the 2014 conference held under the auspices of Hemochromatosis Australia. 2578 96