Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary haemochromatosis is an autosomal recessive disease that is genetically expressed by excessive accumulation of iron in the tissues, resulting in cirrhosis, diabetes mellitus, cardiomyopathy and hypogonadism. As the disease may be diagnosed before the appearance of symptoms, and prevented by repeated phlebotomies, there are strong implications for adoption of a screening procedure. Determinations of transferrin saturation (TS) and serum ferritin concentration (SF) were used to screen 4302 blood donors, who were selected for follow-up studies if they fulfilled any of the following three criteria: (i) TS greater than or equal to 0.7; (ii) TS greater than or equal to 0.5 together with SF greater than or equal to 150 micrograms l-1; (iii) SF greater than or equal to 300 micrograms l-1. A total of 58 subjects who fulfilled at least one of these criteria were reinvestigated, after which 18 individuals still fulfilled at least one criterion. Fifteen subjects having SF greater than or equal to 300 micrograms l-1 were offered liver biopsy and thirteen of these accepted. In one individual, no stainable iron was detected, and two subjects did not fulfil the previously established diagnostic criteria for the diagnosis of hereditary haemochromatosis. Ten subjects who had a high TS and liver iron grade 2-4 according to Bassett were classified accordingly as homozygotes. On the basis of these results, the prevalence of haemochromatosis in Denmark was estimated to be 0.0037-0.0046.
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PMID:Screening for haemochromatosis: prevalence among Danish blood donors. 189 49

The possibility of a metabolic chronic liver disease must always be borne in mind since in certain cases treatment can prevent the lesions from getting worse. The clinical and biochemical context should suggest either (1) genetic haemochromatosis when faced with high serum iron and ferritin levels and elevated transferrin saturation or with a suggestive clinical context (melanoderma, diabetes, hypogonadism, arthropathy, myocardiopathy); or (2) Wilson's disease in young subjects, especially in the presence of neurological and ocular signs or of haemolytic anaemia; or (3) porphyria in case of cutaneous manifestations caused by exposure to sun light. Hence the importance of full clinical examination in patients with chronic liver disease.
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PMID:[Metabolic cirrhosis (hemochromatosis, Wilson's disease, erythropoietic protoporphyria)]. 206 17

We studied pituitary-gonadal function in 11 male and 5 female patients, aged 12-30 yr, with severe beta-thalassemia and chronic iron overload. All had normal basal serum cortisol, T4, and PRL concentrations and normal serum cortisol and GH responses to insulin-induced hypoglycemia and TSH responses to TRH. Of the 11 male patients (all over 17 yr of age), only 3 attained full pubertal development and 4 had subnormal serum LH and FSH responses to GnRH. As a group, their mean basal serum testosterone (T) level was low [11.7 +/- 4.9 (+/- SE) nmol/L; normal, 10-40 nmol/L], and 9 of the 11 male patients responded to hCG with a rise in serum T. Two of the 3 female patients over 17 yr of age were prepubertal with undetectable serum estradiol (E2) levels and absent serum LH and FSH responses to GnRH; the other female patient had regular menstrual cycles and normal serum E2 levels and LH and FSH responses to GnRH. Six of the prepubertal patients (4 males and 2 females, aged 17-30 yr) were studied serially for 3 yr after the start of chelation therapy. Despite a fall of median serum ferritin from 11,910 to 1,303 pmol/L, there was no progression of puberty, and their basal and GnRH-stimulated serum LH and FSH and serum T or E2 levels did not change. Three of these patients (1 male and 2 female) then received pulsatile sc GnRH therapy in addition to chelation therapy for 6 months with no improvement. We conclude that chronic iron overload in patients with severe thalassemia leads to variable degrees of hypogonadotropic hypogonadism, which do not respond to chelation therapy given late in the course of the disease. The hypogonadism in most patients was due to pituitary hyporesponsiveness to GnRH.
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PMID:Hypogonadotropic hypogonadism in severe beta-thalassemia: effect of chelation and pulsatile gonadotropin-releasing hormone therapy. 249 34

To test the hypothesis that deficiencies in hypothalamic-pituitary function in genetic hemochromatosis result from cellular injury by iron deposits, we conducted provocative tests in 11 men with genetic hemochromatosis before and after iron depletion by serial phlebotomy and in 10 control subjects. We gave combination intravenous injections of insulin (0.15 U/kg), luteinizing hormone releasing hormone (LHRH, 100 micrograms), and thyrotropin releasing hormone (400 micrograms) and then measured plasma glucose, growth hormone, corticosteroids, follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone at 30-minute intervals for 90 minutes. Phlebotomy caused a substantial decrease in median values for serum ferritin, deferoxamine-chelatable iron, and hepatic iron concentration. Before phlebotomy, stimulation by hypoglycemia and thyrotropin releasing hormone caused significantly less secretion of growth hormone (P = 0.004) and prolactin (P = 0.03) in patients than in control subjects. No significant improvement was noted, however, in growth hormone or prolactin secretion after phlebotomy. Of the 11 patients, 7 had secondary hypogonadism, and phlebotomy did not improve the serum testosterone, follicle-stimulating hormone, luteinizing hormone, or responses to LHRH in any case. Chlorpromazine injections failed to elevate serum prolactin in all patients, and administration of levodopa caused a partial reduction in serum prolactin; thus, the hypothalamus may be an important locus of endocrine malfunction in these patients. We conclude that abnormal hypothalamic-pituitary function in genetic hemochromatosis is not substantially improved by iron-depletion therapy.
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PMID:Influence of phlebotomy treatment on abnormal hypothalamic-pituitary function in genetic hemochromatosis. 310 26

We identified 35 homozygotes for hemochromatosis through pedigree studies. Thirteen were asymptomatic. Arthropathy was present in 20, hepatomegaly in 19, transaminasemia in 16, skin pigmentation in 15, splenomegaly in 14, cirrhosis in 14, hypogonadism in six, and diabetes in two. No homozygote was in congestive failure. Only one had the triad of hepatomegaly, hyperpigmentation, and diabetes. Serum iron was increased in 30 of 35, transferrin saturation was increased in all 35, serum ferritin in 23 of 32, urinary iron excretion after deferoxamine in 28 of 33, hepatic parenchymal cell stainable iron in 32 of 33, and hepatic iron in 27 of 27. Iron loading was 2.7 times greater in men than in women. No female had hepatic cirrhosis. Diagnosis of asymptomatic hemochromatosis is important because organ damage may be prevented by early therapy. Clinical diagnosis of early hemochromatosis is difficult. Persons with unexplained elevation of transferrin saturation should be studied for hemochromatosis.
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PMID:Homozygosity for hemochromatosis: clinical manifestations. 743 83

Delayed puberty and hypogonadism are frequently observed in patients with homozygous beta-thalassaemia. We evaluated the pituitary-testicular axis in 30 thalassaemic men, aged from 17 to 35 years who were regularly transfused and underwent chelation therapy, while emphasis was given to pituitary reserves of gonadotrophins and the correlation of hormones with serum ferritin (SF). The investigation included endocrinological examination, evaluation of serum basal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone and gonadotrophin-releasing hormone (GnRH) test and also spermiograms. According to the results, patients were divided into three groups: group A, which included 18 eugonadal patients with moderately elevated SF, group B which included six patients who had hypogonadotrophic hypogonadism and excessive elevation of SF, and group C, which included six patients characterized as intermediate, with regard to sexual maturation and SF levels. In conclusion, beta-thalassaemia major leads to variable pituitary iron overload and thus hypophyseal damage. This endocrine disturbance is becoming less frequent nowadays with early and intensive chelation therapy.
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PMID:Pituitary-testicular axis in men with beta-thalassaemia major. 892 Oct 62

The incidence of endocrine dysfunction in relation to the detailed genotype of beta-thalassaemia is investigated in this study. In addition, the association of genotype to specific clinical features of beta-thalassaemia is examined, together with the relationship between serum ferritin levels and endocrine complications. Ninety-seven patients were included, all with transfusion dependent beta-thalassaemia. Patients were divided into 2 categories; group 1 consisted of patients with a beta0/beta0 genotype with or without a concomitant alpha-globin gene deletion as well as patients with beta0/beta+ or beta+/beta+ genotype and normal alpha-globin chain synthesis. Group 2 included patients with beta+/beta+ or beta+/beta0 genotype and one alpha-globin chain deletion and those with a moderate amount of beta-globin chain synthesis (beta++) and normal alpha-globin chain synthesis. The results showed that group 1 patients were more likely to have severe clinical disease (p=0.005). Sixty-four patients (66%) had at least 1 endocrine disorder and 39 (40%) had multiple endocrinopathies; the most common abnormality was hypogonadotrophic hypogonadism (HH). There was a significant association between patients with group 1 genotypes and the presence of HH and impaired glucose tolerance or diabetes. A positive correlation was demonstrated between serum ferritin concentrations and the presence of thyroid or parathyroid dysfunction.
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PMID:Incidence of endocrine complications and clinical disease severity related to genotype analysis and iron overload in patients with beta-thalassaemia. 929 54

Although delay in onset of puberty is a common cause of growth failure in adolescent thalassaemic patients, growth retardation could also be due to iron overload, the toxic effects of desferrioxamine, or the development of other endocrinopathies such as GH insufficiency or primary hypothyroidism. Abnormal body proportions with truncal shortening are commonly seen and could be due to the disease itself, iron toxicity, delay in puberty or the toxic effects of desferrioxamine. The absence of a pubertal growth spurt during spontaneous or induced puberty is detrimental to the achievement of a normal final adult height. Low serum IGF-I and normal GH reserve in short thalassaemic children imply that a state of relative GH resistance exists. The rise in IGF-I and improvement in growth with GH therapy suggest that this GH resistance is only partial. Although the results of short-term GH therapy are encouraging, the impact of treatment on final height of non-GH deficient short thalassaemic children remains uncertain. Multiple endocrinopathies, including hypogonadism, hypothyroidism and diabetes mellitus, occur mainly in older patients who tend to have high serum ferritin levels. Prognosis for survival is greatly improved if the serum ferritin is kept below 2000 micrograms/l by regular chelation. Chelation therapy initiated early before the accumulation of a significant iron burden or dosages of desferrioxamine in excess of 50 mg/kg/day should be avoided. Serum ferritin should be checked regularly and the "toxicity index" should be used to monitor chelation therapy. In cases of delayed puberty, sexual development should be induced at an appropriate age.
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PMID:Growth, puberty and endocrine function in beta-thalassaemia major. 936 50

We studied survival and disease complications in 1,146 patients with thalassemia major, born from January 1, 1960 to December 31, 1987. At last follow-up, in March 1997, probability of survival to age 20 years was 89% and to age 25 years was 82% for patients born in the years 1970-1974. Patients who died had a serum ferritin level, measured the year before death, significantly higher than those who survived. Diabetes was present in 5.4% of the patients; heart failure in 6.4%; arrhythmias in 5.0%, thrombosis in 1.1%, hypothyroidism in 11.6%, HIV infection in 1.8%. Hypogonadism was diagnosed in 55% of 578 patients who had reached pubertal age: 83.5% of hypogonadic females and 78.6% of males were receiving substitutive hormonal therapy. In conclusion, the survival of patients with thalassemia major is good and improving, but the prevalence of severe complications is still high.
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PMID:Survival and disease complications in thalassemia major. 966 44

Genetic haemochromatosis (GH) is one of the most common hereditary diseases, with a prevalence of 1-5/1000 in the Western world. In 90 per cent of cases a mutation is found in an MHC-class-like gene designated HFE, involving a substitution at position 282 of the HFE protein and resulting in defective binding of beta(2)-microglobulin. Animals with beta(2)-microglobulin deficiency develop iron overload, indicating this protein to be involved in the regulation of iron metabolism. Hepatic iron overload results in increased production of oxygen free radicals and peroxidation of membrane lipids, thus causing damage to lysosomes, mitochondria and the endoplasmic reticulum. These cellular events may progress to cell death, fibrogenesis, and the development of liver cirrhosis which is associated with a 200-fold increase in risk of hepatocellular carcinoma. In addition to the risk of diabetes, arthralgia, cardiac arrhythmia, pituitary insufficiency and hypogonadism, iron excess is also associated with aggravation of the cytotoxic effects exerted on hepatocytes by other agents such as alcohol or hepatotrophic viruses. The treatment of iron overload in GH consists of weekly venesection until the serum ferritin level is normalized, followed by maintenance therapy. Survival rates are normal if the disease is detected and treated before complications have developed.
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PMID:[Defective iron metabolism in genetic hemochromatosis. The mechanisms remain unknown in spite of genetic advances]. 972 62


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