SEARCH · Search PubMed

Results for “HEMOCHROMATOSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

PubMed2005

Hemochromatosis gene HFE Cys282Tyr mutation analysis in a cohort of Northeast German hospitalized patients supports assumption of a North to South allele frequency gradient throughout Germany.

Hereditary hemochromatosis is the most common autosomal recessive disease in populations of Northern European ancestry. Population studies demonstrated highly variable frequencies of the HFE Cys282Tyr allele in various regions throughout Europe and decreasing allele frequencies from north to south. However, most of the German prevalence studies covered the central and southern regions of the country. The present study recruited 709 consecutive patients at the time of their admission to a Northeast German University Hospital Medical Department. Polymerase chain reaction-based assays were used to detect HFE Cys282Tyr and His63Asp alleles. Biochemical profiling consisting of transferrin saturation rate, and concentrations of ferritin, transferrin, and iron were performed in Cys282Tyr homozygotes and Cys282Tyr/His63Asp heterozygotes, respectively. Results were compared with previous German prevalence studies. Analysis of 709 Caucasian patients resulted in 650 (91.7%) homozygous HFE wild-type carriers, 55 (7.74%) Cys282Tyr heterozygotes, 4 (0.56%) Cys282Tyr homozygotes and 6 (0.85%) Cys282Tyr/His63Asp compound heterozygotes. The HFE Cys282Tyr allele frequency was 4.44%. Phenotypic markers of iron overload were elevated in one homozygote. We conclude that in contrast to previous hemochromatosis prevalence studies in Germany using blood donors or employees, the present study involving hospital patients estimated a HFE Cys282Tyr allele frequency of 4.44% and supports the emerging concept of an allele gradient decreasing from North to South within Germany.

Adolescent↗

PubMedDate not supplied

Hereditary hemochromatosis: genetics, pathogenesis, and clinical management.

Recent findings have led to major advances in our understanding of genetics and pathophysiology of hereditary hemochromatosis. Many crucial genes and molecules have come to light, and the complex interrelationships between them are being studied. However, several questions still remain unanswered. Availability of genotyping has changed the approach to diagnosis, and serum markers hold promise for prognostication. However, the effectiveness of population screening continues to be an area of controversy.Finally, there is a promise of development of newer therapeutic modalities based on our understanding of the mechanism of iron absorption. In this review, we describe the current state of understanding in the clinical features, pathophysiology and treatment of hereditary hemochromatosis.

Antimicrobial Cationic Peptides↗

PubMed2006

[Mutations of hemochromatosis gene in volunteer blood donors and Chilean porphyria cutanea tarda patients].

In patients with porphyria cutanea tarda (PCT), hepatic iron accumulation associated to hereditary hemochromatosis (HH) could play a role in the etiology and in the clinical expression of the disease. The H63D and C282Y mutations of the HFE gene frequency were studied in a PCT group of patients and compared with the frequency observed in a group of volunteer blood donors. PCT patients were cataloged as hereditary or acquired PCT carriers, whether or not they presented uroporphyrinogen decarboxilase gene mutations. Fifty percent of PCT patients were carriers of the disease's genetic type. Such percentage is significantly higher than what other authors have previously informed. H63D and C282Y mutations were present in 23% and 2.4% of the volunteer blood donors, respectively. Similar frequencies were informed by others authors in Chilean white ethnic populations, and also in Spaniard and Argentinean populations, but significantly higher than that observed in Chile's Araucanean aboriginal population. Probably the frequency of H63D and C283Y mutations are related to the Spaniard ascendancy dominance of Chile's white ethnic population. The frequency of HFE gene mutations in PCT patients was not different than what was observed in volunteer blood donors. Similarly, there was no statistical difference in the frequency of these mutations among patients with acquired or genetic PCT disease. With the obtained results, it is not possible postulate an association between PCT and the hereditary hemochromatosis of HFE gene mutations carrier conditions.

Blood Donors↗

PubMedDate not supplied

Hereditary hemochromatosis: recent advances in molecular genetics and clinical management.

BACKGROUND AND OBJECTIVE: Hereditary hemochromatosis (HC) is an inborn error of iron metabolism leading to increased intestinal iron absorption and progressive iron overload. There have been definite advances in our knowledge of the pathogenesis and management of idiopathic hemochromatosis in recent years, which prompted us to review this subject. INFORMATION SOURCES: The material examined in the present review includes articles and abstracts published in the journals covered by the Science Citation Index and Medline. In addition, both authors have been working in this field for several years and have contributed twelve of the papers cited in the references. STATE OF ART AND PERSPECTIVES: The disease is a late onset autosomic recessive condition, especially frequent in Caucasians. If unrecognized, severe clinical symptoms develop in mid-life related to organ failure. Early diagnosis prevents complications, since an intensive phlebotomy course removes excess iron and offers patients a normal life expectancy. Transferrin saturation is the first examination step, but liver biopsy is still essential for diagnosis and prognosis of HC. The biochemical defect is unknown. Positional cloning of the HC gene has led to the isolation of all the candidate region on the short arm of chromosome 6, telomeric to HLA-A. Recently a putative HC gene has been cloned from this region and found to be mutated in a large proportion of patients. The gene, known as HLA-H, is an atypical MHC class I gene. Although its biological function remains unknown, HLA-H is the first strong HC candidate gene. Molecular screening of patients and carriers is now possible in a significant portion of cases, thereby permitting better control of the disease. If it is unequivocally confirmed that the HLA-H gene is responsible for the disease, understanding of its biological function will provide information on the type and activity of the involved protein, revealing new insights into iron uptake and metabolism in humans.

Adult↗

PubMed1998

Heterozygosity for the C282Y mutation in the hemochromatosis gene is associated with increased serum iron, transferrin saturation, and hemoglobin in young women: a protective role against iron deficiency?

Genetic hemochromatosis (GH) is the most common autosomal-recessive disorder (1 in 300 in populations of Celtic origin). Homozygosity for a C282Y mutation in the hemochromatosis (HFE) gene is the underlying defect in approximately 80% of patients with GH, and 3. 2-13% of Caucasians are heterozygous for this gene alteration. Because the high frequency of this mutation may result from a selection advantage, the hypothesis was tested that the C282Y mutation confers protection against iron deficiency in young women. To address this question the genotype of codon 282 was determined in a cohort of 468 unrelated female healthcare workers, ages 18-40 years. In all study participants, a complete blood count was obtained, and erythrocyte distribution width, serum iron, transferrin, transferrin saturation, and ferritin were measured. Two individuals were homozygous for the C282Y mutation, 44 were heterozygous, and 416 were homozygous for the wild-type allele. Heterozygous women had significantly higher values for hemoglobin (P = 0.006), serum iron (P = 0.013), and transferrin saturation (P = 0. 006) than women homozygous for the wild-type allele. Our data provide evidence for a protective role of the C282Y mutation in the HFE gene against iron deficiency in young women and suggest that a more efficient utilization of nutritional iron may have contributed to the high prevalence of the mutation in Caucasian populations.

Adolescent↗

PubMed2004

Minor salivary gland biopsy in neonatal hemochromatosis.

BACKGROUND: Neonatal hemochromatosis (NH), a rare disorder seen in newborns, is defined as liver failure with extrahepatic iron deposition that spares the reticuloendothelial elements. This disorder is considered the pathologic end point of a variety of diseases that result in prenatal liver failure, and mortality without aggressive treatment is common. However, ready diagnosis remains a problem. A liver biopsy specimen showing siderosis is not specific for hemochromatosis and may be risky in patients with coagulopathy. OBJECTIVE: To describe a safe and effective method for diagnosing NH that uses lower-lip minor salivary gland biopsy and can be readily performed even in the most severe cases of coagulopathy under local anesthesia. METHODS: Eleven neonates with suspected NH were identified. After informed consent, a biopsy specimen of lower-lip tissue was taken under local anesthesia by the otolaryngology team. RESULTS: Ten of the 11 neonates had minor salivary gland tissue present (or detected) by initial frozen-section analysis. One of the 11 patients required a second biopsy owing to a lack of sufficient minor salivary gland tissue on the initial specimen, underscoring the importance of frozen-section analysis. Six of 7 neonates with NH had positive biopsy findings and the seventh had a false negative. There were 4 true negatives. Three of 7 children with NH survived, 1 requiring liver transplantation and 2 with medical treatment only. CONCLUSION: Minor salivary gland biopsy is a safe and effective way to quickly diagnose NH, a rapidly progressive, often fatal condition.

Biopsy↗

PubMed1997

Tricho-hepato-enteric syndrome: further delineation of a distinct syndrome with neonatal hemochromatosis phenotype, intractable diarrhea, and hair anomalies.

We report on two sibs with syndromal congenital iron storage disease. Prenatal symptoms were IUGR, hydramnios, and placental hyperplasia. Clinical anomalies included hypertelorism and sparse, thin, curly hair (trichomalacia). Clinical course was marked by intractable diarrhoea, with normal histological and enzymological studies, cholestatic jaundice, hepatomegaly appearing after 30 days, and progressive liver failure, leading to death after a few months. The only metabolic anomaly was progressive hypermethioninemia. Pathologic examination of both children showed a similar pattern of multivisceral iron deposit compatible with a diagnosis of neonatal hemochromatosis: extensive liver fibrosis or cirrhosis with nodular regeneration, cholestasis, ductular proliferation, and hepatic, pituitary, thyroidal, adrenal, and pancreatic iron deposition. The unusual course for neonatal hemochromatosis in both sibs combined with concordant extrahepatic anomalies suggest that they could have a specific iron storage syndrome with possible autosomal recessive inheritance, probably similar to the sibship reported by Stanckler et al. [Arch Dis Child, 57:212-216, 1982].

Amino Acid Metabolism, Inborn Errors↗

PubMed1998

Factors affecting the rate of iron mobilization during venesection therapy for genetic hemochromatosis.

Although progressive iron accumulation is a characteristic feature of genetic hemochromatosis, the factors affecting the rate of iron mobilization by venesection have not been established. Venesection records were analyzed in 77 hemochromatosis homozygotes to study the factors affecting the rate of iron mobilization by venesection. The rate of iron mobilization was the iron removed divided by the time required to deplete iron stores (serum ferritin < 50 microg/L). Mean duration of venesection therapy was 1.4 years (range 0.44-3.6 years). All patients completed the therapy and there were no significant adverse effects. Rate of iron mobilization was higher in cirrhotics compared to non-cirrhotic patients (P = 0.04). Iron mobilization was inversely related to intestinal radioiron absorption (r = -0.45, P = .01). There was no significant relationship between iron mobilization and patient age, gender, serum ferritin, and hepatic iron concentration. Iron mobilization is increased in cirrhotics and patients with lower intestinal iron absorption. Venesection therapy is safe and well tolerated in all age groups.

Adult↗

PubMed1999

Elevated parathyroid hormone 44-68 and osteoarticular changes in patients with genetic hemochromatosis.

OBJECTIVE: To determine whether the osteoarticular changes associated with genetic hemochromatosis could be explained by metabolic parathyroid hormone (PTH) disorders. METHODS: The study involved 210 patients with liver iron overload syndromes. Osteoarticular changes were numerically scored as the number of damaged joints. PTH 1-84 and 44-68 were assayed. RESULTS: An increase in serum PTH 44-68 levels was found in one-third of untreated patients who had no calcium or PTH 1-84 abnormalities. Serum PTH 44-68 levels correlated positively with serum ferritin levels. In multivariate analyses, the number of affected joints correlated positively with age, serum PTH 44-68 levels, and serum ferritin levels. CONCLUSION: Liver iron overload syndromes, especially genetic hemochromatosis, are associated with elevated circulating levels of PTH fragments containing the 44-68 region, which appears to play a role in osteoarticular changes. This increase seems to be a consequence of iron overload.

Adolescent↗

PubMed2005

T-cell large granular lymphocytic leukemia and hereditary hemochromatosis: a fortuitous association?

We describe a patient with hereditary hemochromatosis (homozygous for C282Y mutation) and neutropenia who was found to have underlying T-cell large granular lymphocytic (T-LGL) leukemia. The diagnosis was confirmed by demonstrating T-cell receptor (TCR) gene rearrangement by polymerase chain reaction (PCR). Multiple quantitative and qualitative defects have been described for the T cells of patients with hemochromatosis. Although the association between the two may be fortuitous, this case report raises the possibility that the T cells in these patients may be susceptible to leukemic transformation as well.

Female↗

PubMed1985

Transferrin sialic acid contents of patients with hereditary hemochromatosis.

Recent evidence suggests that asialotransferrin may enhance hepatic uptake of trivalent metal ions through the asialoglycoprotein-receptor pathway. In hereditary hemochromatosis, there is preferential uptake of iron by hepatocytes. We purified transferrin from two patients with this disease. Their transferrins had normal electrophoretic patterns and contained normal amounts of sialic acid. We conclude that the preferential uptake of iron by hepatocytes in hereditary hemochromatosis is not due to the presence of asialotransferrin in their plasma.

Asialoglycoproteins↗

PubMed1991

Sickle cell disease and hemochromatosis.

A 50 year-old patient with sickle cell anemia was seen who had received only two units of blood during his lifetime. He had marked iron overloading, cirrhosis of the liver, arthralgia, and mild glucose intolerance. We believe the iron overloading was associated with hereditary hemochromatosis rather than sickle cell anemia because he had HLA-A3 and B7 antigens, and hepatic iron deposits were primarily in parenchymal cells rather than Kupfer cells. The coexistence of either homozygous or heterozygous hemochromatosis should be suspected in sickle cell patients with organ damage from iron overloading.

Anemia, Sickle Cell↗

PubMed1994

Prevalence of abnormal iron studies in heterozygotes for hereditary hemochromatosis: an analysis of 255 heterozygotes.

Iron studies were compared in 434 patients from 80 hemochromatosis families classified as putative homozygotes, heterozygotes, and normal by HLA typing. There were 28 of 255 (11%) heterozygotes with an elevated serum ferritin and 22 of 255 (8.6%) with an elevated transferrin saturation. Serum ferritin (140 +/- 10.2 micrograms/liter; mean +/- standard error) was greater in heterozygotes than in normal subjects (87 +/- 8.5 micrograms/liter; P < .05, Mann Whitney test). Transferrin saturation was greater in heterozygotes (38% +/- 0.88%) than in normal patients (29% +/- 1.1%; P < .0001). Mean hepatic iron concentration was 54 +/- 6 mumol/g (n = 17), and the hepatic iron index was < 2 in these patients. Most heterozygotes for hemochromatosis have a normal serum ferritin and transferrin saturation. Heterozygotes with minor elevations in serum ferritin or transferrin saturation do not have significant iron overload as assessed by hepatic iron concentration.

Female↗

PubMed1989

Genetic hemochromatosis: distribution analysis of six laboratory measures of iron metabolism.

Six laboratory measures of iron metabolism were studied in a control sample, and a family sample was ascertained on the basis of probands with clinically diagnosed genetic hemochromatosis. The respective distribution of each variable evidenced a mixture of components, presumably arising from the segregation of an HLA-linked locus for hemochromatosis. There were significant differences in the distributional characteristics with respect to sex and genotype-specific variances. These aspects of the data have important implications for subsequent segregation and linkage analyses, which traditionally assume homoscedasticity and homogeneity of the genetic effect.

Deferoxamine↗

PubMed1990

Iron storage disease in parents and sibs of infants with neonatal hemochromatosis: 30-year follow-up.

Neonatal hemochromatosis (NH), an uncommon and generally fatal disorder of infancy, is defined by hepatic disease of antenatal onset, generally manifest at birth, and by stainable iron in a tissue distribution like that seen in heritable adult-onset hemochromatosis (HH). It is not known if parents and sibs of infants with NH are at risk of iron storage disease in later life. We provide 30-year follow-up for iron overload of a family in which 6 of 9 children died in utero or early in the neonatal period. Four of the 6 came to autopsy, where severe liver disease was found; in 3 of the 4, autopsy material could be reviewed. These 3 children had NH. Studies 30 years later did not identify HH or other iron storage disease in the parents or surviving sibs. These findings suggest that first-degree relatives of persons with NH are not necessarily at increased risk of iron storage disease in later life.

Aging↗

PubMed2002

High headache prevalence among women with hemochromatosis: the Nord-Trøndelag health study.

In this large cross-sectional population-based study, 51,272 persons responded to a headache questionnaire and were screened for hemochromatosis. Phenotypic hemochromatosis and the C282Y/C282Y genotype were both associated with an 80% increase in headache prevalence evident only among women. The reason for this association is unclear, but one may speculate that iron overload alters the threshold for triggering a headache by disturbing neuronal function.

Adult↗

PubMed1992

Survival and prognostic factors in 212 Italian patients with genetic hemochromatosis.

Two hundred twelve Italian patients with genetic hemochromatosis (181 men, mean age 50 +/- 11 yr; and 31 women, mean age 49 +/- 10 yr) were followed for a median period of 44 mo (range = 3 to 218 mo). Alcohol abuse was present in 31 subjects (15%), and chronic HBV and HCV infection were seen in 19 (9%) and 35 (24%) of 145 cases tested, respectively. Twenty-four patients (11%) had concomitant beta-thalassemia trait. Liver biopsy revealed cirrhosis in 146 and a noncirrhotic pattern in the other 66. Perls' stain was degree III in 37 patients and IV in 171 patients. One hundred eighty-five patients underwent weekly venesection, and iron depletion was achieved in 122 cases after total iron removal of 3 to 41 gm. Death occurred in 44 patients after 3 to 198 mo and was due to hepatocellular carcinoma in 20 cases, liver failure in 10, extrahepatic cancer in six, heart failure in three and hemochromatosis unrelated causes in five. Cancer has developed in seven other patients still alive (hepatocellular in five and extrahepatic in two). No deaths were observed among noncirrhotic patients; cumulative survival rates in cirrhotic patients were 85%, 75%, 60% and 47% at 3, 5, 8 and 10 yr, respectively. Univariate analysis in the 146 cirrhotic patients showed that age greater than 60 yr, alcohol abuse, cardiomyopathy, skin pigmentation, portal hypertension, hypoalbuminemia, hypergammaglobulinemia and Child class B or C had significant negative prognostic value. At multivariate analysis, only alcohol abuse, gamma-globulins greater than 2.0 gm/dl and Child class B or C maintained their negative prognostic values (p less than 0.01, hazard ratio 2.7; p less than 0.001, hazard ratio 2.8; and p less than 0.001, hazard ratio 4.3, respectively).

Adult↗

PubMed1995

Portal hypertension and iron depletion in patients with genetic hemochromatosis.

Clinically, portal hypertension has been considered to be less common and less severe in patients with cirrhosis resulting from iron overload in homozygotes for genetic hemochromatosis than in patients with cirrhosis of other causes. To characterize the prevalence and progression of portal hypertension in genetic hemochromatosis (GH), 120 cirrhosis and iron-overloaded patients were compared with a control group of 120 patients with postnecrotic cirrhosis (PNC) who were matched for gender, age, Child's class, and alcohol abuse. Gastroesophageal endoscopy and abdominal ultrasonography were performed at diagnosis and repeated every 12 months and every 6 months, respectively, to evaluate the presence and severity of varices, the caliber of the portal vein and its collaterals, and splenic size. At diagnosis a similar frequency of varices was observed in patients with GH (25%) and in PNC (24%), as well as of portal vein abnormalities and spleen enlargement. During the follow-up period, all but two of the patients with GH were treated by phlebotomy and depleted of excess iron. After a mean of 6 +/- 4.3 (SD) years of observations (range, 2 to 10 years), varices were improved or completely reversed in 26% of patients with cirrhosis and GH but in only 5% of those with PNC (P < .01). Bleeding from varices was observed in only one patient with GH but in five patients with PNC. Of 22 patients with GH in whom portal hypertension was unmodified or worsened, 16 had coexistent hepatic viral infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗