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What then are the lessons to be learned about prevention and treatment of hemochromatosis? Early diagnosis is essential. The best indicator would be testing of serum iron and total saturation followed by a serum ferritin if elevated. Once these indices are abnormally high, MRI and or a liver biopsy should confirm the stage of the iron over-loaded state. If indeed the patient is not iron-overloaded (normal liver biopsy in the face of high saturation and ferritin level) phlebotomies should be performed until these indices are normal and then maintained at a normal level. This should entail four to six phlebotomies a year. Family members should also be screened and managed in a like manner. HLA typing may be a partially helpful screening device. The abnormal gene is closely linked on chromosome 6 with HLA histocompatibility loci. Now, by means of HLA typing, we can identify heterozygote carriers and homozygous (abnormal) among first degree relatives of patients with hemochromatosis. Unfortunately, HLA typing can only be used within a given family and cannot be used to screen the general population. It is estimated that 70% of hemochromatoics have the antigen HLA-A3; however, so does 28% of the (well) general population. Patients with unexplained cirrhosis, arthritis, liver disease, diabetes, impotency, cardiomyopathy and neurological symptoms should be screened in a like manner. Routine health practice profile chemistries must include a serum iron and iron saturation, and if high followed by a serum ferritin. Once diagnosed, therapy must be maintained with phlebotomy for the life time of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemochromatosis: diagnosis and treatment. 179 61

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

During the period 1950-1985, a total of 179 cases of clinically overt hereditary haemochromatosis (HH) were registered in Denmark, 140 males and 39 females. Median age at diagnosis was 55 years (range 29-81). Diagnostic approaches, symptoms and physical signs at discovery are described. All patients had grade 3-4 liver haemosiderin iron, and cirrhosis was present in 84%. Serum (S-) transaminase was elevated in 92%, S-alkaline phosphatase in 47% and S-bilirubin in 23%, while plasma prothrombin time was below normal in 34%. Females had higher alkaline phosphatase than males (p less than 0.05). Bone marrow haemosiderin iron (n = 81) showed no relation to iron status indicators and was unsuitable as a diagnostic tool. Skin biopsy (n = 56) was positive for haemosiderin iron in 67% and for melanin in 57%, but was of limited value in the assessment of HH. Arthropathy was registered in 44%; arthralgias and clinical joint abnormalities occurred more frequently in females than in males (p less than 0.05). Latent diabetes mellitus was found in 34% and overt diabetes in 55%, being more frequent in males than in females (p less than 0.05). Other endocrine abnormalities were seen in 66%. Cardiac failure was observed in 9% and abnormal ECG in 35%. Males had higher haemoglobin (p less than 0.0001) and S-iron (p less than 0.01) than females, while S-transferrin, transferrin saturation, S-ferritin and mobilizable iron stores showed no significant sex differences. Median transferrin saturation was 87% (range 52-100); values greater than 62% were observed in 96% of the patients. Median S-ferritin was 3,400 micrograms/l (800-12,700) and median iron stores 14.8 g (4.5-36.4).
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PMID:Hereditary haemochromatosis in Denmark 1950-1985. Clinical, biochemical and histological features in 179 patients and 13 preclinical cases. 191 39

Hemochromatosis was recognized as an iron-storage disease for 50 years before it was proposed to treat it by removing hemoglobin. Davis and Arrowsmith are credited with the first report that demonstrated its value. Larger series have provided statistically valid evidence of improved quality of life and increased longevity. The earlier the disease is discovered, the less risk of morbidity and mortality. Screening tests (serum iron, total iron-binding capacity, serum ferritin) are recommended for all blood relatives of index cases of this hereditary disease and for all clinics where complications of hemochromatosis may be treated: liver disorder however mild, diabetes mellitus, heart disease, arthropathies, sterility, impotence, premature menopause, and abnormal pigmentation of the skin.
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PMID:A history of phlebotomy therapy for hemochromatosis. 199 28

Plasma levels of retinol binding protein (RBP), prealbumin, total protein, albumin, transferrin and ferritin were estimated in three groups of diabetic patients seen at a diabetes centre in S. India. The groups consisted of patients with fibrocalculous pancreatic diabetes (FCPD), non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). Mean RBP levels were lower in FCPD and IDDM patients compared to controls but this did not reach statistical significance. Prealbumin levels were normal in FCPD patients, but low in IDDM compared to controls (P less than 0.005) and NIDDM (P less than 0.05). FCPD patients had lower transferrin levels compared to controls (P less than 0.05). There were no differences in the levels of total protein, albumin and ferritin in any of the study groups. The study shows that biochemical evidence of undernutrition is seen in FCPD and IDDM patients while NIDDM patients are not significantly different from non-diabetic control subjects.
Diabetes Res Clin Pract 1991 Mar
PMID:Nutritional profile of fibrocalculous pancreatic diabetes and primary forms of diabetes seen in southern India. 203 42

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

Diabetes mellitus is found with increased frequency in patients with both primary and secondary hemochromatosis. In these conditions, the pancreas shows fibrosis and iron overload of acini, interstitium, and islet B cells. Previous morphological studies have only described changes found in advanced stages of disease, while abnormalities of the initial stage of iron overload have, as yet, not been reported. Rats fed a carbonyl iron-supplemented diet for 4-15 months showed storage iron deposition (ferritin and hemosiderin) in many organs, in a pattern similar to primary human hemochromatosis. Electron microscopic examination of the pancreas showed ferritin particles segregated in lysosomes of acinar cells, as well as diffuse cytosiderosis of macrophages in the interstitial septa. In the islets, iron deposits were discrete and only in B cells. In the absence of electron-microscopic studies of incipient pancreatic cytosiderosis in human subjects, the present experimental animal study may contribute to a better understanding of the pathway leading to the extensive lesions found in the advanced stages of the human iron overloading diseases.
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PMID:Ultrastructural changes in the pancreas of carbonyl iron-fed rats. 218 17

We assessed the prevalence of previously unrecognized hemochromatosis among patients in whom diabetes mellitus was diagnosed after the age of 30 yr, and we evaluated the positive predictive value of biochemical screening tests for hemochromatosis in diabetic subjects. Thirty-eight of 572 patients screened (6.6%) had a serum ferritin level greater than 324 micrograms/L; 16 patients had normal levels on repeat testing. Four patients' serum ferritin levels fell to less than 400 micrograms/L. Seven of 18 patients with a persistently elevated serum ferritin level did not undergo a liver biopsy because of a recognized cause of hyperferritenemia (carcinoma, alcoholism, or systemic lupus erythematosus). The diagnosis of hemochromatosis seemed certain in 1 of 3 patients who were not biopsied for technical reasons. Of 8 patients biopsied, 2 had hemochromatosis, 4 had fatty liver, 1 had hemosiderosis, and 1 had a chronic inflammatory cell infiltrate with no iron deposition. Of 4 patients with a raised transferrin saturation level, 2 had raised serum ferritin levels and hemochromatosis, 1 had raised serum ferritin and hemosiderosis on liver biopsy, and 1 had a normal transferrin saturation level on repeat testing. Two of 3 cases of hemochromatosis had other clinical markers of the condition. Therefore, routine screening of diabetic patients for hemochromatosis is not necessary, because patients with hemochromatosis will often have other clinical features of the disease. When screening diabetic patients for hemochromatosis, it should be remembered that a persistently raised serum ferritin level has a low positive predictive value (16.6%) and that a normal transferrin saturation level does not exclude the diagnosis.
Diabetes Care 1990 May
PMID:Usefulness of biochemical screening of diabetic patients for hemochromatosis. 235 Oct 33

Because chronic hypoxemia causes a redistribution of iron from serum and storage pools into an expanding erythrocyte mass, and because infants of diabetic mothers are often hypoxemic in utero and have a high prevalence of polycythemia at birth, we studied iron distribution in 43 term infants of diabetic mothers. Twenty-four infants were at an appropriate size for gestational age; 19 were large for gestational age. At birth, 28 infants (65%) had abnormal serum iron profiles; eight had decreased ferritin concentrations only (stage 1), nine had decreased ferritin and increased total iron-binding capacity values (stage 2), and 11 had these serum findings plus elevated free erythrocyte protoporphyrin concentrations (stage 3). The hypoglycemic infants who were large for gestational age (n = 14) had a higher prevalence of abnormal iron profiles than euglycemic infants who were appropriate in size for gestational age (n = 20; 93% vs 50%; p = 0.009). Progressively abnormal iron profiles were associated with higher glycosylated fetal hemoglobin values, greater degrees of macrosomia, increased hemoglobin and erythropoietin concentrations, and increased erythrocyte/storage iron ratios. Erythropoietin concentrations were inversely linearly correlated with serum iron values (n = 32, r = -0.54; p = 0.003). The combined erythrocyte and storage iron pools were significantly lower in infants with abnormal iron values whose mothers were diabetic, particularly in infants of women with confirmed diabetic vasculopathy. We speculate that these findings are likely due to (1) increased fetal iron utilization during compensatory hemoglobin synthesis in response to chronic hypoxemia and (2) reduced iron transfer during late gestation complicated by diabetes.
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PMID:Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. 239 4

After 6 months on hemodialysis, a 58-year-old male patient with diabetes developed photosensitive bullous dermatosis on his hands and face. There was no evidence of liver diseases although the patient had a history of excessive alcohol consumption. He was suspected to have iron overload in the liver. Analysis of porphyrins in plasma, hemofiltrate, urine and feces by high performance liquid chromatography revealed significantly high levels in these samples with a porphyrin profiles which is consistent with porphyria cutanea tarda. The fluorometric assays of plasma also disclosed an elevated plasma porphyrin level. And it seemed that there were correlation between the fluctuation of vesicle formation, serum ferritin level and plasma porphyrin level. Small volume plasma exchange temporarily reduced the plasma porphyrin level and prevented vesicle formation.
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PMID:[Porphyria cutanea tarda in a chronic hemodialysis patient]. 239 21


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