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Restless legs syndrome (RLS) occurs in some persons with iron deficiency, and some persons with RLS benefit from oral iron therapy. Approximately one in 200 persons of northern European ancestry have hemochromatosis attributable to inheritance of two common mutations of the hemochromatosis-associated HFE gene on chromosome 6. We evaluated and treated a 46-year-old man with RLS who was diagnosed as having hemochromatosis after he developed new symptoms associated with taking iron therapy for RLS. He had transferrin saturation 88%, serum ferritin 658 ng/ml, and C282Y homozygosity. Therapeutic phlebotomy of one unit of blood (450-500 ml) weekly (total 24 units) relieved his non-RLS symptoms, caused RLS symptoms to occur more frequently, and was associated with transient fatigue and mild dependent edema. His sister, who also has RLS, was subsequently diagnosed as having hemochromatosis. We conclude that serum transferrin saturation and ferritin levels should be measured before initiation of iron therapy of RLS. Patients with a history of iron deficiency or low serum iron parameters should undergo evaluation for iron deficiency; patients who have histories suggestive of hemochromatosis or iron overload or elevated pre-treatment transferrin saturation or serum ferritin levels should undergo evaluation to determine the cause of these abnormalities before they are treated with iron. In all persons with RLS treated with oral iron, serum iron parameters should be re-measured once or twice yearly during therapy.
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PMID:Hemochromatosis and iron therapy of Restless Legs Syndrome. 1131 89

Allogenic blood transfusion may be required for the treatment of anemia due to a hematologic disease, the consequences of chemotherapy or other circumstances, such as haemorrage and/or surgery. Transfusion becomes indispensable to prevent the side effects of anemia, such as hypoxia, palpitations, tachycardia, cardiac ischemia and fatigue. However, frequent transfusions can cause several acute problems such as hemolysis, anaphylactic shock and septic shock but also chronic problems such as iron overload (hemochromatosis), alloimmunisation and metabolic disturbances. Each of these complications can produce serious consequences and could even be sometimes fatal. Therefore we should recognise, prevent and if necessary treat all these hazards. Our article emphasises the potential chronic problems. For hemochromatosis, an iron chelator (deferoxamine) should be administered. In the presence of allo-immunisation the more compatible ABO blood group must be chosen and blood products be eliminated by filtration, when there has been blood reaction. When an allo-graft of hematopoitic tissues is considered an irradiation of blood products is necessary. Research is being carried out to develop substitute products for transfusion (haemoglobine solutions) or molecules acting on the syntheses of haemoglobine (butyrate arginine). The efficacy of erythropoitine, (EPO) is well recognised for stimulation of haemoglobine syntheses in renal failure and oncology.
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PMID:[Surveillance and side-effects of transfusions]. 1218 32

Iron overload in body tissues can cause complications such as cirrhosis, cardiomyopathy, diabetes, hypogonadism and arthritis. In populations of northern European descent, most iron overload is due to hereditary haemochromatosis (HHC), a genetic condition that causes increased iron absorption. HHC can be treated or prevented by regular phlebotomy treatments. Some experts have called for population screening for HHC, so that early phlebotomy treatment can be initiated. Two screening tests are available: measurement of the serum iron transferrin saturation (Tf%) and genetic testing for HFE mutations. However, both methods have low positive predictive values. Current data suggest that most people at risk are unlikely to develop clinical symptoms and that the population prevalence of clinical complications of HHC is low, arguing against population screening. Two other prevention strategies are available. (1) Health provider education, to heighten awareness of HHC as an explanation for symptoms and signs seen in early iron overload including unexplained fatigue, joint pain, palpitations, abdominal pain, elevated liver function tests, hepatomegaly and elevated serum ferritin. (2) Family-based testing after a diagnosis of HHC, to ensure that relatives are evaluated for evidence of iron overload. More research is also needed to identify the factors that increase risk for disease in persons with excess iron uptake, to determine whether moderate iron overload is a health risk and to evaluate the causes of iron overload other than HHC.
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PMID:Hereditary haemochromatosis: a realistic approach to prevention of iron overload disease in the population. 1240 10

Genetic haemochromatosis is an autosomal recessive inherited disorder of iron metabolism due to mutation of the HFE gene. In homozygotes (1 in 300 of the UK population), this results in excessive iron absorption from the gut and its deposition in major body organs. This may give rise to fatigue, arthritis, cardiac failure, diabetes mellitus, hepatic cirrhosis or skin pigmentation, occurring predominantly in males over 50 years of age. Identification uses measurement of serum iron, iron-binding capacity (or transferrin) and ferritin, together with initial or confirmatory genetic DNA studies.
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PMID:Genetic haemochromatosis. 1242 71

In a 49-year-old man and a 28-year-old woman, both of whom complained of fatigue, HFE-gen related respectively non-HFE-gen related primary haemochromatosis was diagnosed, based on the elevated serum transferrin saturation, the elevated serum ferritin levels, DNA studies and liver biopsy with qualitative respectively quantitative iron measurements. Their complaints diminished after bloodletting. Three women respectively 64, 61 and 46 years of age, were also suspected of primary haemochromatosis. The latter two presented with complaints of fatigue and malaise and chronic hepatitis C respectively. All three showed an elevated serum transferrin saturation and serum ferritin concentration. Further investigation showed the presence of secundary iron overload. Causes for it being excessive alcohol consumption, overweight and a poorly regulated diabetes mellitus type 2, and chronic hepatitis C respectively. These patients received specific therapy. Primary haemochromatosis is a common disorder of iron metabolism in individuals of Northern European descent. Diagnosis is based on an elevated serum transferrin saturation in combination with both elevated serum ferritin levels and homozygosity for the Cys282Tyr-mutation in the HFE-gen. The presence of an elevated serum transferrin saturation in combination with an elevated serum ferritin level is not always sufficient for the diagnosis, since these may be affected by other disorders. Moreover, iron overload may be caused by a form of haemochromatosis that is not HFE-related. In case of doubt as to the diagnosis, histological examination of the liver with a qualitative or quantitative iron determination is the golden standard.
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PMID:[Diagnosis of 5 patients with possible primary hemochromatosis]. 1271 48

HFE-associated hereditary haemochromatosis is a recessive, iron-overload disorder that affects about one in 200 north Europeans and that can be easily prevented. However, genetic screening for this disease is controversial, and so we assessed whether such screening was suitable for communities. Cheek-brush screening for the Cys282Tyr HFE mutation was offered to individuals in the workplace. Outcomes were assessed by questionnaires before and after testing. 11,307 individuals were screened. We recorded no increase in anxiety in individuals who were homozygous for the Cys282Tyr mutation or non-homozygous. Self-reported tiredness before testing was significantly higher in homozygous participants than in non-homozygous participants (chi2 test, p=0.029). Of the 47 homozygous individuals identified, 46 have taken steps to treat or prevent iron accumulation. Population genetic screening for HFE-associated hereditary haemochromatosis can be practicable and acceptable.
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PMID:Use of community genetic screening to prevent HFE-associated hereditary haemochromatosis. 1603 15

Chondrocalcinosis can be associated with hyperparathyroidism, hemochromatosis, hypophosphatasia, and hypomagnesemia. Gitelman syndrome (GS), an inherited disorder due to loss of function mutations of the gene encoding the distal convoluted tubule Na-Cl cotransporter (NCCT), is characterized by hypokalemia metabolic alkalosis, hypomagnesemia, and hypocalciuria. A 53-year-old man, with history of recurrent joint effusions and pains affecting knees and wrists, had transient episodes of muscle pain, weakness, cramping, and fatigue over a one-year period. Laboratory tests showed hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia related to genetically proven GS. Radiographs of affected joints revealed calcium pyrophosphate dihydrate deposition. This observation points out the necessity to look for Mg depletion (and especially GS) in the biological investigation of chondrocalcinosis. Additionally, the association between GS (NCCT inactivation) and high bone mineral density provides a new insight into the possible role of thiazides in osteoporosis management.
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PMID:Chondrocalcinosis secondary to hypomagnesemia in Gitelman's syndrome. 1614 86

Most studies on health related quality of life (HRQoL) of chronic liver patients were done in small clinical populations or restricted to one aetiology or disease stage. There is still a need for a study in a large liver patient population with various aetiologies and disease stages, approaching a population-based study. We evaluated the impact of liver disease aetiology on generic HRQoL, disease-specific HRQoL and fatigue and we compared HRQoL and fatigue between aetiological groups and healthy Dutch controls. Members of the Dutch liver patient association completed the Liver Disease Symptom Index, Short Form-36, and Multidimensional Fatigue Index-20. We compared the HRQoL between patients with viral hepatitis, autoimmune hepatitis, cholestatic diseases, hemochromatosis and other liver diseases by linear, ordinal and logistic regression, corrected for disease stage and other significant factors. Viral hepatitis patients showed a worse mental health than other aetiological groups. Hemochromatosis patients demonstrated 17% more bodily pain than viral hepatitis patients and the strongest decrease in role emotional health with increasing age. Aetiological groups showed a worse generic HRQoL and more fatigue than controls. In conclusion, viral hepatitis and hemochromatosis patients have a more impaired HRQoL than patients of other liver disease aetiological groups.
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PMID:Generic and disease-specific health related quality of life of liver patients with various aetiologies: a survey. 1733 30

A couple was investigated for subfertility. Haemochromatosis was suspected when the 36-year-old man had failure of ejaculation, fatigue and limited facial hair growth. Haemochromatosis was confirmed by an iron saturation of 102% (normal range: 20-45), a highly elevated serum ferritin concentration of 5468 mg/1l (normal range: 18-280) and highly elevated liver enzymes. Molecular genetics showed homozygous C282Y mutation of the HFE gene. Due to consequent venesection therapy, levels of ferritin and transferrin decreased and liver enzymes normalized. However luteinizing hormone and follicle stimulating hormone failed to increase to normal levels. Treatment with gonadotropins was then applied, which corrected ejaculation and semen characteristics. His partner failed to become pregnant with ovulation stimulation and intrauterine inseminations. After two unsuccessful IVF procedures she became pregnant in the third procedure. Haemochromatosis should be considered and iron studies performed if subfertility due to an endocrine disorder is being investigated. Deposition in the pituitary or the gonads of the HFE-mutated patients leads to hypogonadism. Most of the patients with C282Y mutation are homozygous (85-90%), but the majority of the carriers will not develop the disease. Deficiency of hepcidin, an important regulator for the iron metabolism, was suspected in our patient, based on the early onset of his disease and the low serum levels of hepcidin. The age at diagnosis and the start of venesections is critical for reversal of organ damage. Aggressive venesection can restore hypothalamic-pituitary-gonadal function, preventing further organ damage. But with increasing disease progression venesection will not restore azoospermia or the failure to ejaculate.
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PMID:[Anejaculation caused by haemosiderosis: male infertility in hereditary haemochromatosis]. 1763 84

HFE-related hereditary haemochromatosis (HH) is an iron overload disease attributed to the highly prevalent homozygosity for the C282Y mutation in the HFE gene. The pathophysiology of this error in iron metabolism is not completely elucidated yet, although deficiency of the iron regulatory hormone hepcidin appears to play a role. Ways of diagnosing iron overload include measurement of the serum iron parameters, i.e. serum transferrin saturation and serum ferritin, by a liver biopsy or by calculating the amount of mobilisable body iron withdrawn by phlebotomies. Clinical signs attributed to HFE-related HH include liver failure, arthralgia, chronic fatigue, diabetes mellitus and congestive heart failure. organ failure can be prevented by phlebotomies starting before irreversible damage has occurred. Therefore, screening to facilitate early diagnosis is desirable in individuals at risk of developing HFE-related iron overload. over time it appeared that the clinical penetrance of the HFE mutations was much lower than had previously been thought. This changed the opinion about a suitable screening modality from case detection, via population screening, to family screening as the most appropriate method to prevent HFE-related disease. However, before the implementation of family screening it is vital to have thorough information on the relevance of the specific health problem involved, on the clinical penetrance of C282Y homozygosity and on the effectiveness of the screening approach.
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PMID:Changing aspects of HFE-related hereditary haemochromatosis and endeavours to early diagnosis. 1807 64


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