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Idiopathic hemochromatosis is one of the most common adult genetic disorders in the Caucasian population. The clinical manifestations are various with hepatic, pancreatic, cardiac disorders.... Arthritis associated with idiopathic hemochromatosis are less well-known and differential diagnosis with other arthropathies is sometimes difficult. Early diagnosis enables rapid treatment and better prognosis.
The discovery of the hemochromatosis gene has deeply changed and simplified the diagnosis of the disease. In a given individual, establishing the diagnosis relies, from now on, on a simple blood sample showing the couple: elevated transferrin saturation and homozygous C282Y mutation (= C282Y +/+). Liver biopsy should only be performed when iron overload is massive in order to detect cirrhosis (or bridging fibrosis), i.e. in a prognostic view. Practically, liver biopsy is confined to the following two situations: when the C282Y +/+ patient exhibits hepatomegaly and/or an increase in serum transaminases and/or a serum ferritin level above 1,000 micrograms/L; whenever, despite a strong bio-clinical suspicion of iron overload, genetic testing does not show the expected homozygosity for C282Y. At the family level, evaluating the risk for hemochromatosis is now "instantaneous" thanks to genetic testing. One must, however, keep in mind in interpreting the data of the family members that: clinical expression of the homozygous status is not constant; heterozygosity for C282Y does not per se lead to significant iron overload, but may constitute a co-factor exacerbating (or increasing the risk of) other hepatic or non hepatic diseases. Heterozygosity exposes also to the risk of homozygosity among the offspring; this knowledge of C282Y status must be balanced by the negative impact from the standpoint of possible societal genetic discrimination.
Hereditary hemochromatosis (HHC) is one of the most common inherited disorders in the Caucasian population. Diagnosis usually made after an elevation in ferritin and serum transferrin saturation is noted, often accompanied by asymptomatic hepatomegaly. Diagnosis is confirmed by genetic testing or liver biopsy. Damage to organs is due to excessive intestinal iron, which is transported to and then deposited in the liver parenchyma, and the heart, skin, and endocrine organs, causing skin pigmentation, development of cirrhosis and hepatic carcinoma, diabetes and endocrine failure, and heart failure. Bony changes can be manifested by arthritis, often in non-weight-bearing joints. The treatment of HHC is phlebotomy, which depletes iron stores. When diagnosis is made before organ damage occurs, treatment can prevent manifestations of the disease. Skin pigmentation and some cardiac damage may reverse on depletion of iron stores, but liver and endocrine damage is rarely reversible. Arthropathy is also not reversible, and often continues to progress even with effective treatment. When hemochromatosis is diagnosed, all first degree relatives of the patient should undergo genetic testing. With early detection and treatment this can be a manageable chronic disease. If undetected, it is potentially fatal.
A primary mechanism of radiation-induced DNA damage is by generation of free radicals. Chronically increased oxidative stress from elevated levels of iron in the body may increase radiation sensitivity by decreasing cellular oxygen radical scavenging capability. Hemochromatosis heterozygotes have elevated body iron. Low-level radiation sensitization by iron may be particularly pertinent for risk of breast cancer. Since 10% of the population appears to be heterozygous for the hemochromatosis gene, a radiosensitizing effect would have pervasive implications.
An autopsy case of congenital infantile myofibromatosis and neonatal hemochromatosis is reported. A thirty-six-hour-old baby girl had multiple subcutaneous nodules in addition to multiple visceral involvement of heart, lungs, pharynx, larynx, stomach, small bowel, large bowel, pancreas, kidneys, spleen, thyroid, adrenal glands, lymph nodes, peripheral nerves, meninges and soft tissues. In these tumoral nodules, three types of histological patterns were observed: 1-hemangiopericytoma-like, 2-mixed, and 3-pure spindle cell. Tumor cells were immunohistochemically positive for actin, and negative for desmin, muscle-specific antigen, and estrogen, related protein. The histological and immunohistochemical findings of the case suggested that a close relationship may exist between infantile myofibromatosis and infantile hemangiopericytoma. In addition to infantile myofibromatosis, neonatal hemochromatosis characterized by iron deposition in parenchymatous organs such as liver, pancreas, lungs, thyroid, and adrenal glands was another important characteristic of the case.
Neonatal hemochromatosis (NH) is a rare clinical-pathologic entity defined by severe neonatal liver failure (NLF) of intrauterine onset associated with extrahepatic siderosis that spares reticuloendothelial elements. Whether this entity is the result of a distinct disease process or is the pathologic end-result of many other forms of NLF remains to be assessed. Death from multisystem organ failure usually occurs in the first few days or weeks of life. We report two sisters with neonatal hemochromatosis with different outcome. The first died at 21 days of life for multiorgan failure and sepsis. The second was diagnosed and treated very early by aggressive support with fresh-frozen plasma, packed red cells, platelets, coagulation factors, diuretics, and pressors, and she is well at 2-year-follow-up. The few therapeutic options are discussed. In general, few patients survived NH. Among patients treated only by medical approachs and that did not undergo orthotopic liver transplantation (OLTX), favorable outcome is only very rarely reported. For management of NH infants early recognition of the disease is critical. Our experience seems to suggest that as early is the start of treatment as high is the possibility of survival. At this moment very early aggressive supportive treatment should appear to be the most useful approach to stabilize the patient hoping in spontaneous liver recovery, or, in turn, to permit OLTX before septic complications bring to clinical decline.
The relative distribution of storage iron between bone marrow and liver has not been adequately studied in patients with iron-loading disorders. To help clarify this we assessed iron metabolism in patients with iron overload and in control subjects with cirrhosis but no excess body iron. In 4 patients with advanced iron overload studied late in the course of their illness, excess hemosiderin was present in both bone marrow and liver, as expected. In contrast, 2 patients with idiopathic hemochromatosis whose excess iron had been depleted by phlebotomy subsequently developed progressive hepatic parenchymal and reticuloendothelial (RE) deposition of iron, yet marrow hemosiderin remained sparse. Moreover, surface radioactivity over the liver after an oral dose of 59Fe. These results suggest that during the initial stages of hemochromatosis there is a dissociation in the rate of iron accumulation between the bone marrow and liver. Excess hemosiderin appears to be deposited predominantly and preferentially in hepatic storage sites until the later stages of the disease.
Hemochromatosis is an autosomal recessive disorder that causes abnormal absorption of iron and results in iron overload. This disorder affects the liver, pancreas, heart, and endocrine systems, and if undetected and untreated, organ damage and death can result. The recent discovery of the gene associated with hemochromatosis has led to increased awareness of the disease and controversy over its diagnosis and treatment. Transferrin saturation is the best laboratory assay to detect the disease, and a liver biopsy is required to confirm a diagnosis. Current treatment involves therapeutic phlebotomy and iron-chelating agents. Information on diet modifications and genetic counseling for people affected with this disease should be included in patient education.
Hemochromatosis is a common genetic disease in which early diagnosis and treatment results in an excellent long-term prognosis. Population screening projects have been completed that included iron tests and genetic testing. In this review, the controversial issues surrounding population screening for hemochromatosis are explored in the context of available information from large screening studies.
We report a 64 years old male, admitted for dyspnea and edema of two weeks duration. A sideroblastic anemia, requiring multiple transfusions, was diagnosed four years earlier. The chest X-ray showed an enlarged heart and right pleural effusion. A low left ejection fraction was evidenced by echocardiogram. Doppler analysis of the mitral flow revealed a restrictive hemodynamic pattern. A diagnosis of secondary cardiac hemochromatosis deposit was made. Nine days after admission the patient died due to heart failure. The clinical presentation of cardiac hemochromatosis as a sudden and irreversible heart failure, as well as the importance of early diagnosis and surveillance of high-risk patients is emphasized.
Hemochromatosis results when the body's iron stores progressively increase. Surplus iron stored in body tissues leads to organ dysfunction and death. Warnings that elevated iron stores increase the risk of cancer development necessitate a review of this condition. Two types of hemochromatosis, hereditary and secondary, are diagnosed in today's hematology-oncology practices. Distinguishing the differences with respect to etiology and management is essential to the risk assessment and long-term nursing management of this patient population.
The case of a 43-year-old male is presented, with diagnosed diabetes mellitus,heart failure, skin pigmentation, hepatic cirhosis, and hereditary hemochromatosis confirmed by liver biopsy. The objective of this publication is to have hemochromatosis in mind as a differential diagnosis in a middle-aged patient with several pathologies and organs involved.
Hereditary hemochromatosis was diagnosed in three asymptomatic siblings following the unexpected finding of elevated serum iron concentrations. This diagnosis was confirmed by hepatic biopsy. Repeated phlebotomies resulted in a significant decline of serum iron and ferritin concentrations and a decrease of hepatic iron content. This report and a review of the literature indicate that the diagnosis of hereditary hemochromatosis must be considered more frequently in childhood. Organ dysfunction from iron overload may be minimized in children by the early commencement of regular phlebotomy.
Hereditary hemochromatosis has been redefined over the past century, from a rare (but often fatal) disorder of iron overload known as "bronzed diabetes" to only biochemical evidence of altered iron metabolism, and recently to mere expression of the C282Y homozygous genotype of the HFE gene. The variable definitions of the disease, as well as the variable degree of penetrance of the C282Y homozygous genotype, have made it difficult to determine optimal screening strategies. Multiple studies performed since discovery of the C282Y mutation have led to the conclusion that overall penetrance of the genotype is low and that screening of asymptomatic general populations for hereditary hemochromatosis is not recommended. Screening for HFE mutations among certain patient groups, including patients with cirrhosis, however, may help target those who would benefit most from iron removal. For most patients, phlebotomy is the preferred treatment option; iron chelation therapies are available for patients unable to tolerate phlebotomy.
BACKGROUND: Hereditary hemochromatosis is commonly due to two HFE1 (Histone Family E1) gene mutations - H63D and C282Y. Mutations in the Asian Indians are less well studied. AIMS: The aim of this preliminary study was to find out the prevalence of HFE gene mutations in nonviral liver cirrhosis patients. SETTINGS AND DESIGN: Unexplained liver cirrhosis cases with transferrin saturation> 45%, attending the gastroenterology clinic in the years 2004 and 2005 were subjects of the prospective study. Asymptomatic individuals with negative family history of hemolytic anemia or liver disease served as controls. MATERIALS AND METHODS: The clinical presentation was recorded in the patients. Transferrin saturation was estimated by standard colorimetric technique. The two common mutations in HFE1 gene and Y250X mutation of TFR (transferrin receptor) gene were studied by polymerase chain reaction based methods. RESULTS: A majority of the cases were sporadic, but family history was positive in four patients. In one family with multiple affected members, there was clear evidence of autosomal dominant inheritance. Seven out of 31 (22.6%) of unexplained cirrhosis cases were positive for mutations. One was homozygous for H63D. In healthy controls, prevalence was 8.1% (6/74). None of the patients or controls was positive for C282Y mutation of HFE1 or Y250X of TFR gene. CONCLUSIONS: Thus, in a number of cases of hemochromatosis in Indians, a gene with dominant inheritance may be involved in causation of the phenotype. The prevalence of HFE mutations in Indians is comparable to that reported from neighboring countries. It is worth studying other mutations in HFE gene and other iron overload genes in cryptogenic cirrhosis cases.
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)
Neonatal hemochromatosis (NH), a generally fatal disorder of infancy, is characterized by severe hepatic insufficiency of intrauterine onset and by marked organ iron loading. Its cause is unknown. It has been suggested that NH may represent an unusual manifestation of hereditary hemochromatosis (HH), which is human leukocyte antigen (HLA) linked. Evidence for major rearrangements or deletions at the HLA class I region and at three loci directly involved in iron metabolism (H- and L-apoferritin and the transferrin receptor [TfR]) was sought. The population studied included five probands with NH and 14 first-degree family members in a total of six kindreds. Also sought were HLA associations with NH by collating the results of HLA serotyping in these 19 persons and in 17 members of 7 additional kindreds in which NH has occurred, including 5 probands with NH and 12 first-degree family members. We found no evidence for major rearrangements or deletions in H- or L-apoferritin genes, in TfR genes, or within the HLA locus. We found no evidence for linkage of NH to HLA serotypes. We conclude that while NH and HH are similar in their patterns of iron loading, they are not genetically related.
A 60-year-old man is reported with idiopathic hemochromatosis and type III hyperlipoproteinemia. Regular phlebotomy therapy and fenofibrate treatment favorably influenced the disorder of iron metabolism and the lipid disease. Evidence is given that both errors of metabolism are independently inherited diseases, although the symptoms of the first (idiopathic hemochromatosis) may aggravate the expression of the second (type III hyperlipoproteinemia).