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)

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

This review focuses on the management of iron metabolism and iron overload experienced in the hereditary condition, human factors engineering (HFE)-associated hemochromatosis. Hemochromatosis refers to a group of genetic diseases that result in iron overload; the major one globally is HFE-associated hemochromatosis. The evolution in understanding of the most common form of hereditary hemochromatosis, being the substation of cysteine to a tyrosine at position 282 in the HFE gene, has been extensively studied Novel mutations in both HFE and non-HFE genes have been indicated in this disease which hold significance in its application for the Asia-Pacific region. In conditions with iron overload, the storage of excess iron in various body tissues leads to complications and toxic damage. The most common presenting complaint for this disease is malaise, lethargy and other non-specific symptoms. In order to diagnose hereditary hemochromatosis, there are biochemical, imaging and genetic testing options. Currently, cascade screening of affected families is preferred over population-level screening. The mainstay of treatment is venesection and the appropriate approach to treatment has been consolidated over the years. Recently, the indications for venesection therapy of hemochromatosis have been challenged and are the subject of ongoing research.
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PMID:Management of human factors engineering-associated hemochromatosis: A 2015 update. 2700 87