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)

Haemochromatosis is one of the most common inborn errors of metabolism. In prospective epidemiological studies the frequency of haemochromatosis is 0.0037 (76/20333 subjects) for homozygotes which corresponds to a gene frequency of 0.061 and a frequency of heterozygotes of 0.115. Abnormality in liver function tests, weakness and lethargy, skin hyperpigmentation, diabetes mellitus, arthralgia, impotence and ECG abnormalities are the most frequent findings and symptoms at diagnosis. In recent years about 50% of patients were detected without having liver cirrhosis and 20% of patients did not have any symptoms and pathology except iron overload. Survival analyses in long-term studies showed that in the absence of cirrhosis and diabetes, iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. Patients with massive and long-lasting iron overload had a worse prognosis than those with less severe iron excess. Iron removal in general ameliorated liver disease, weakness and cardiac abnormalities, and also prevented the progression of endocrine alterations. Therapy, however, did not influence insulin-dependent diabetes. Most deaths in patients with hereditary haemochromatosis were caused by liver cancers which often occurred many years after complete iron removal. In patients with haemochromatosis, liver cirrhosis, cardiomyopathy, and diabetes mellitus are also significantly more frequent causes of deaths when compared with the general population. Further strategies have to evaluate the design of screening programmes in order to diagnose more patients in the precirrhotic and asymptomatic stage.
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PMID:Clinical spectrum and management of haemochromatosis. 788 Nov 58

Goldberger discovered human pellagra was a non-infectious disease, affecting mostly the small and the timid in overcrowded institutions. Symptoms were diarrhoea, dermatitis and dementia. The staff and older children escaped the disease. They ate the meat and left the small and timid with the gravy. The 'Goldberger syndrome' is observed during competitive feeding of livestock, in ketotic animals and in the zinc depleted which are lethargic and pick all day at their feed. The pellagra preventative factor was later found to be nicotinic acid, derived from the amino acid tryptophan. Deficiencies of copper, magnesium, vitamin B6 (activated by a zinc kinase) inhibit the conversion of tryptophan to nicotinic acid. Stresses, including liver diseases, malabsorption, iron overload, porphyria, marasmus, cold stress, pregnancy, lactation, antibiotics and sulfa drugs, all increase dietary needs of nicotinic acid. Elevated free fatty acids and ketone bodies in the blood are associated with ketosis, zinc depletion and the pre-diabetic state. There is a diminished uptake of glucose by the tissues, a condition also found in parturient paresis of dairy cows when elevated hydrocortisone promotes insulin resistance and hyperglycaemia. This defect in insulin response leads to a diabetic-like state. The major predisposing factor in parturient paresis of dairy cows is hypocalcaemia. Gut absorption of dietary calcium may not meet the primary demands of lactation initiation until bone calcium mobilisation is established.
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PMID:Metabolic disorders of cattle. 839

A 5-year-old girl presented with lethargy, anaemia and facial distortion. Both parents had beta-thalassaemia minor. Radiographs confirmed the characteristic features of thalassaemia major. A treatment regime comprising regular blood transfusions was commenced. The basis of the radiographic changes and the current role of magnetic resonance imaging, particularly with respect to assessing iron overload, are emphasized.
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PMID:Clinics in diagnostic imaging (29). Thalassaemia major with iron overload. 940 69

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 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

Smoking causes a variety of adverse effects on organs that have no direct contact with the smoke itself such as the liver. It induces three major adverse effects on the liver: direct or indirect toxic effects, immunological effects and oncogenic effects. Smoking yields chemical substances with cytotoxic potential which increase necro-inflammation and fibrosis. In addition, smoking increases the production of pro-inflammatory cytokines (IL-1, IL-6 and TNF- alpha) that would be involved in liver cell injury. It contributes to the development of secondary polycythemia and in turn to increased red cell mass and turnover which might be a contributing factor to secondary iron overload disease promoting oxidative stress of hepatocytes. Increased red cell mass and turnover are associated with increased purine catabolism which promotes excessive production of uric acid. Smoking affects both cell-mediated and humoral immune responses by blocking lymphocyte proliferation and inducing apoptosis of lymphocytes. Smoking also increases serum and hepatic iron which induce oxidative stress and lipid peroxidation that lead to activation of stellate cells and development of fibrosis. Smoking yields chemicals with oncogenic potential that increase the risk of hepatocellular carcinoma (HCC) in patients with viral hepatitis and are independent of viral infection as well. Tobacco smoking has been associated with suppression of p53 (tumour suppressor gene). In addition, smoking causes suppression of T-cell responses and is associated with decreased surveillance for tumour cells. Moreover, it has been reported that heavy smoking affects the sustained virological response to interferon (IFN) therapy in hepatitis C patients which can be improved by repeated phlebotomy. Smoker's syndrome is a clinico-pathological condition where patients complain of episodes of facial flushing, warmth of the palms and soles of feet, throbbing headache, fullness in the head, dizziness, lethargy, prickling sensation, pruritus and arthralgia.
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PMID:Heavy smoking and liver. 1703 78

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