Pros & Cons for routine population screening, newborn testing, etc.

Since HH is so easily treated & the outcome is best with an early diagnosis, why are we still not doing routine testing for it?  Routine screening, beginning with all newborns, along with implementation of preventative measures, are desperately needed for this condition!  Insurance companies would surely find it more cost-effective to include an iron profile in their screening programs & treat iron overload in the early stages as opposed to a later diagnosis. 
[It is obvious that I am totally FOR routine screening for HH, but you will also find links here that represent the argument against it, so that you may form your own opinion.]  

Click on the title to read more on this topic.

• A 24-year-old patient with decreased libido and erectile dysfunction as initial manifestations of hemochromatosis Dtsch Med Wochenschr. 2000 Dec 1: In subfertility from an endocrine disorder primary hemochromatosis should be considered in the differential diagnosis. Only early diagnosis and prompt iron depletion may improve the prognosis of these patients.

• ABC of diseases of liver, pancreas, and biliary system Other causes of parenchymal liver disease  BMJ 2001;322:290-292 ( 3 February ) Haemochromatosis is the commonest inherited liver disease in the United Kingdom. It affects about 1 in 200 of the population and is 10 times more common than cystic fibrosis.

• A high prevalence of HLA-H 845A mutations in hemochromatosis patients and the normal population in eastern England. Blood Cells Mol Dis 1997 Aug; We found a gene frequency in 200 normal subjects for teh 845A (C282Y) allele of 0.085, corresponding to a carrier frequency of 17% which is among the highest reported anywhere in the world.  This population will be an excellent model for studies on the penetrance of the 845A homozygous genotype and population screening.

• A history of phlebotomy therapy for hemochromatosis.  Crosby WH. Chapman Cancer Center, Joplin, MO Am J Med Sci 1991 Jan  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.

• Annals of Internal Medicine SUPPLEMENT DIAGNOSIS AND MANAGEMENT 
  Diagnosis of Hemochromatosis, Annals of Internal Medicine, 1 December 1998. 129:925-931.Lawrie W. Powell, MD; D. Keith George, MD; Sharon M. McDonnell, MD; and Kris V. Kowdley, MD

• Answers to your questions about hereditary hemochromatosis
  from The College of American Pathologists (CAP) Dec 18, 2001

• A population based study of the clinical expression of the clinical expression of the Hemochromatosis gene NEJM Sept 1999  Our findings have implications for population screening for hereditary hemochromatosis. 

• Association of mutations in the hemochromatosis gene with shorter life expectancy.
  Arch Intern Med. 2001 Nov 12  In a high-carrier frequency population like Denmark, mutations in HFE show an age-related reduction in the frequency of heterozygotes for C282Y, which suggests that carrier status is associated with shorter life expectancy.

• Asymptomatic hemochromatosis subjects: genotypic and phenotypic profiles 
  Blood, 1 December 2000, Vol. 96, No. 12, pp. 3707-3711;  Ronald L. Sham, Richard F. Raubertas, Caroline Braggins, Joseph Cappuccio, Margaret Gallagher, and Pradyumna D. Phatak;  From the Department of Medicine, Rochester General Hospital, the Mary M. Gooley Hemophilia Center Inc, and The University of Rochester School of Medicine and Dentistry, Rochester, NY; and The Centers for Disease Control and Prevention, Atlanta GA.  Our study demonstrates that TS screening will identify many individuals with only modest degrees of iron loading who may not meet traditional phenotypic diagnostic criteria but who have genotypes associated with iron loading. Those with lower degrees of iron overload are less likely to be C282Y homozygotes. 

• Biochemical liver profile in hemochromatosis. A survey of 100 patients. 
  J Clin Gastroenterol 1991 Jun; We find that mild abnormalities in the biochemical liver profile are common in hemochromatosis and suggest that patients with an unexplained abnormality in the liver profile should be screened for hemochromatosis with a serum ferritin and transferrin saturation.

• Classification and diagnosis of iron overload 
  Haematologica 1998 May The recent description of new conditions associated with iron overload and the identification of the genetic defect of hereditary hemochromatosis prompted us to review this subject and to redefine the diagnostic criteria of iron overload disorders.

• Clinical and genetic aspects of hereditary hemochromatosis,
  Pathologe 2001 May. As laboratory parameters for measuring HH lack specificity, and HH remains asymptomatic for a long time, methods for genetic screening are highly valuable.

• Clinical aspects of hemochromatosis. Transfus Sci. 2000 Dec Brissot P, Guyader D, Loreal O, Laine F, Guillygomarc'h A, Moirand R, Deugnier Y. The diagnosis can, from now on, be ascertained on the sole association of a plasma transferrin saturation (TS) over 45% and homozygosity for the C282Y mutation. Liver biopsy is only required to search for cirrhosis whenever there is hepatomegaly and/or serum ferritin >1000 ng/ml and/or elevated serum AST.

• Clinical Consequences of New Insights in the Pathophysiology of Disorders of Iron and Heme Metabolism Hematology 2000  The American Society of Hematology The screening strategy could be based on the assessment of serum transferrin saturation in adults aged 18 or more. Genetic testing testing for C282Y would be confined to individuals with transferrin saturation > 45%. This strategy would then avoid the ethical, logistical, and financial problems raised by systematic genetic testing as well as the societal impact of discovering a genetic mutation in asymptomatic persons without a disease. It is, in fact, essential that major changes occur in the attitudes towards unexpressed or slightly expressed HFE homozygosity, especially by insurers and health care administrators, to avoid any adverse genetic discrimination.

• Clinical experience with early hemochromatosis Tidsskr Nor Laegeforen. 1994 Jun [Article in Norwegian] We conclude that fasting serum-iron and transferrin should be determined in all subjects over 40 years of age and in patients with chronic elevation of liver enzymes

• Clinical management of iron overload.
  Gastroenterol Clin North Am. 1998 Sep HHC is a common inherited disorder, characterized by iron accumulation in the liver, heart, pancreas, and other organs. The clinical consequences of systemic iron loading are diverse and not always improved with iron reduction therapy.

• Clinical spectrum and management of haemochromatosis 
  Baillieres Clin Haematol 1994 Dec Further strategies have to evaluate the design of screening programmes in order to diagnose more patients in the precirrhotic and asymptomatic stage.

• Clinical Studies of Haemochromatosis  Queensland Institute of Medical  Research, Hepatocellular Cancer Laboratory, Professor Lawrie Powell   Knowledge of haemochromatosis, its prevention, the type and severity of symptoms it causes, the availability and nature of treatment, ability of sufferers to participate in normal activities, and longevity are relevant issues for community education. Members of an informed public can mobilise support for the early diagnosis of haemochromatosis, encourage people to be tested for the disorder and influence the debate about screening.

• Controversy in primary care BMJ 2000;320:1314-1317 ( 13 May )     Should asymptomatic haemochromatosis be treated?  Treatment can be onerous for patient and doctor  Commentary: False certainty of clinical guidance  Commentary: Early treatment is essential

• Current concepts in rational therapy for haemochromatosis.  
  Drugs. 1991 Jun . Venesection should be continued until all excess iron stores are removed as judged by failure of a rise in haemoglobin concentration on cessation of phlebotomy. Screening of first degree relatives should commence from a young age (e.g. 10 years).

• Diabetes and haemochromatosis: current concepts, management and prevention.
  Diabete Metab 1995 Dec Diabetes, a serious complication of haemochromatosis, is frequently associated with cirrhosis which reduces life expectancy

• Diabetes mellitus in hemochromatosis Z Gastroenterol. 1999 Jun  [Article in German] The degree of glucose intolerance and diabetes mellitus in hemochromatosis is closely associated with the stage of iron overload and thus also the stage of the accompanying liver disease. Similar to other liver diseases glucose intolerance due to insulin resistance precedes diabetes mellitus also in hemochromatosis.

• Diagnosis and management of hemochromatosis
  by Dr. Anthony Tavill, Director of the Maurice and Sadie Friedman Center For Digestive Diseases and Liver Disorders, Mathile and Morton J. Stone Professor of Digestive Diseases and Liver Disorders at the Mt. Sinai Medical Center, Professor of Medicine and Nutrition at Case Wetern Reserve University. [Excellent & thorough article of diagnosis & treatment.  This is a pdf file] 

• Diagnosis and management of precirrhotic hemochromatosis Gushurst TP, Triest WE.  Department of Pathology, Cabell Huntington Hospital, West Virginia. W V Med J 1990 Mar  Three cases of hemochromatosis in the precirrhotic stage of the disease are presented. The pathophysiology, clinical and laboratory features and management are discussed. The high gene frequency in the general population warrants routine screening tests in asymptomatic healthy young adults.

• Diagnosis and treatment of genetic hemochromatosis Rev Prat. 2000 May 1 [Article in French]
  Moirand R, Guillygomarc'h A, Brissot P, Deugnier Y. The disease can be lethal due to liver disease, carcinoma or heart disease, but life expectancy goes to normal if patients are treated before the occurrence of cirrhosis. Treatment relies on regular venesections. Familial screening is essential.

• Diagnostic confusion caused by hepatitis C: hemochromatosis presenting as rheumatoid arthritis J Rheumatol 1998 Dec We describe a patient with hemochromatosis and coexistent infection with the hepatitis C virus who was initially thought to have rheumatoid arthritis.

• Dietary Iron Supplements - Use or not to use?
  Nutrition Today James R. Connor John L. Beard 05-06-1997 There is little reason to support a general need for iron supplementation in the diet at any age. Perhaps this article and review of supplementation pros and cons should conclude with a new interpretation of an old saying: "It is better to wear out than to rust out;" don't expose your system to more iron than it needs.

• Disease-Related Conditions in Relatives of Patients with Hemochromatosis
  Zaneta J. Bulaj, M.D., Richard S. Ajioka, Ph.D., John D. Phillips, Ph.D., Bernard A. LaSalle, B.S., Lynn B. Jorde, Ph.D., Linda M. Griffen, B.A., Corwin Q. Edwards, M.D., and James P. Kushner, M.D.  Volume 343:1529-1535  November 23, 2000  Number 21  In conclusion, our data emphasize the importance of screening relatives of persons with hemochromatosis.

• DNA testing for haemochromatosis: diagnostic, predictive and screening implications.
  Pathology 2000 Nov The range of DNA testing available includes: (1) diagnostic, (2) predictive (also called presymptomatic testing) and (3) screening.

• End-stage liver disease without hemochromatosis associated with elevated hepatic iron index.
  J Hepatol. 1998 Aug;29 Cotler SJ, Bronner MP, Press RD, Carlson TH, Perkins JD, Emond MJ, Kowdley KV.  Department of Medicine, University of Washington, Seattle, USA. (i) Serum transferrin saturation and hepatic iron index lack specificity for hereditary hemochromatosis in end-stage liver disease. (ii) Genotyping for Cys 282 Tyr may provide the best method to identify hereditary hemochromatosis in the setting of end-stage liver disease.

• Ferritin Physiology Overview of the function of ferritin with a section on hemochromatosis.

• FINAL DIAGNOSES:  A case of Hereditary Hemochromatosis with dilated cardiomyopathy, micronodular cirrhosis, history of chronic alcoholism from Department of Pathology, University of Pittsburgh School of Medicine.

• Genetic Haemochromatosis:   A guideline on Diagnosis & Therapy compiled on behalf of the Clinical Task Force of the  British Committee for Standards in Haemotology  2/2000 [a pdf file]

• Genetic Health-What Is Hemochromatosis? By Amanda Ewart Toland, PhD  Reviewed by Chris Friedrich, MD, PhD Last updated September 1, 2000

• Genetic hemochromatosis, a Celtic disease: is it now time for population screening?  Genet Test 2001 Summer;The high C282Y allele frequency in the Irish population together with its close linkage to HH indicate that C282Y genotyping is the preferred screening strategy for this disease in Ireland.

• Genetic test for hemochromatosis debated Study results show that a phenotype test alone does not always detect this blood disorder's genetic mutation. AMNews staff. Sept. 25, 2000

• Haemochromatosis and HFE gene.
  Acta Gastroenterol Belg. 1999 Oct-Dec The practical management of haemochromatosis has been greatly modified, since liver biopsy is no more necessary for diagnosis in C282Y homozygotes, and is only needed for exclusion of cirrhosis. Family screening has also greatly benefited from genotyping.

• Haemochromatosis as an endocrine cause of subfertility. 
  BMJ 1998;316:915-916 ( 21 March ) Clinical review.  Lesson of the week.   Haemochromatosis is well established as a cause of infertility in both men and women, usually because iron deposition in the pituitary or the gonads leads to hypogonadism.  As haemochromatosis is a fairly common disorder it should be considered when subfertility from an endocrine disorder is being investigated.

• Haemochromatosis: iron still matters. Intern Med J 2001 May-Jun Our ability to detect those predisposed to haemochromatosis is greatly enhanced by testing for HFE mutations. Although the precise definition of iron overload is debated, a diagnosis of haemochromatosis cannot be made without demonstrating increased body iron stores.

• Haemochromatosis may present as exercise related joint pains without arthropathy, early treatment improving outcome, Case reports including x-ray pictures of hips, hands, knees. CLINICAL REVIEW Lesson of the week: Ian McCurdie and J David Perry BMJ 1999

• Hemochromatosis  
  Powell LW, Yapp TR  Clin Liver Dis 2000 Feb:  It is now apparent that iron, even in the modest tissue concentrations, can act as a co-factor in potentiating cell injury in other liver diseases.

• Hemochromatosis: A Common, Rarely Diagnosed Disease
  By Vincent J. Felitti, MD, FACP  Commentary by David Baer, MD, FACP.  Hemochromatosis is the most common, life-threatening genetic disorder in North America, yet most physicians have never personally diagnosed a case: all see an unrecognized case in their offices every two weeks.

• Hemochromatosis and iron therapy of Restless Legs Syndrome. 
  1389-9457 2001 May; We conclude that serum transferrin saturation and ferritin levels should be measured before initiation of iron therapy of RLS.

• Hemochromatosis and Wilson disease: diagnosis and treatment  
  Chapter 20 in the book: "Evidence Based Gastroenterology and Hepatology"   Paul C. Adams.

• Hemochromatosis arthropathy--an early manifestation of genetic hemochromatosis 
  Z Rheumatol 1997 May-Jun This investigation shows that knowledge of the typical signs of hemochromatotic arthropathy could lead to an earlier diagnosis of genetic hemochromatosis which is necessary to prevent the complications of iron overload in those patients

• Hemochromatosis, A simple genetic trait, Dr. Richard D. Press, Oregon Health Sciences University With the discovery of the causative gene, the disorder stands revealed as America's single most common mendelian disease. Unlike other genetic diseases, it is already curable. Indeed, genetic screening makes it potentially preventable.

• Hemochromatosis at the intersection of classical medicine and molecular biology  
  C R Acad Sci III 2001 Sep

• Hemochromatosis, Cooley Dickinson Hospital Editor: George R Bowers MD CDH Oncology  January 2000 Volume 4: No. 1.   Hemochromatosis is a common, genetically transmitted disease. The diagnosis of hemochromatosis is sometimes difficult and frequently missed. This issue will review the pathogenesis, diagnosis and treatment of this fascinating disease. Ms. Kathy Fleming will review the management of a most troubling complication of therapy---lymphedema. 

• Hemochromatosis: diagnosis and management. Bacon BR.  Gastroenterology 2001 Feb  HFE mutation analysis has strengthened our ability to diagnose HH accurately and is useful in family studies. HFE mutations may play a contributory role in some patients with PCT, NASH, or chronic HCV.

• Hemochromatosis  Gale Encyclopedia of Medicine The symptoms of hemochromatosis include fatigue, weight loss, weakness, shortness of breath, heart palpitations, chronic abdominal pain, and impaired sexual performance. The patient may also show symptoms commonly connected with heart failure, diabetes or cirrhosis of the liver. Changes in the pigment of the skin may appear, such as grayness in certain areas, or a tanned or yellow (jaundice) appearance.

• Hemochromatosis: Gastrointestinal Health Hemochromatosis, the most common genetic disease in the United States, results in iron overload and, if left untreated, severe organ damage. 

• Hemochromatosis: genetics helps to define a multifactorial disease 
  Clin Genet, 54(1):1-9 1998 Jul University of Washington, Seattle 98105 wburke@u.washington.edu  Early detection is desirable, because periodic phlebotomy provides effective treatment for iron overload and may prevent complications of the disorder.

• Hemochromatosis:  Genetics, Pathophysiology, Diagnosis and Treatment, "Introduction to Hemochromatosis"  Part I,  by Barton & Edwards.  Except from their book, [a pdf file] This is a large & excellent book covering all areas of hemochromatosis.  Published in 2000, $225.00

• Hemochromatosis gene variants in three different ethnic populations: effects of admixture for screening programs Hum Biol 2001 Feb  Genetic testing for hemochromatosis may have important implications for diagnosis and screening of the disease.

• Hemochromatosis: HEPATOLOGY WATCH  
  Timely Information for Practicing Physicians.  Info. on their site includes the following topics:

  Elevated Hepatic Iron Index and End-stage Liver Disease
  Hemochromatosis Gene Mutations in Chronic HCV Patients
  Heterogeneity of Hemochromatosis in Italy
  HFE Gene Expression
  HFE Gene Mutations in Chronic Viral Hepatitis Patients
  HFE Genotyping
  Phenotypic Expression of HFE Mutations
  Population screening
  Screening for Hemochromatosis

• HEMOCHROMATOSIS; HFE Mercier et al. (1997) urged strongly that the symbol HFE be used for the hemochromatosis gene rather than 'HLA-H' as used by Feder et al. (1996)

• Hemochromatosis in Ireland and HFE. Blood Cells Mol Dis. 1998  The allele frequency of 14% for the C282Y mutation in our control population is the highest reported and supports the hypothesis of a Celtic origin for the hereditary hemochromatosis gene.

• Hemochromatosis Special  American Liver Foundation newsletter,  ALF Progress, Vol. 21 No. 1, Summer 1999 The ALF newsletter created three scenarios based on the real life ethical, economic and medical quandaries posed by hemochromatosis, and asked three experts from divergent fields to respond with their opinions. The experts are: Bruce R. Bacon, MD [Director, Div. of Gastroenterology & Hepatology, Saint Louis University School of Medicine, St. Louis, M0]; medical ethicist Mark A. Rothstein, Esq. [Director, University of Houston Law Center, Health Law & Policy Institute, Houston, TX] and hemachromatosis patient Gayle Hoffman.

• Hereditary Haemochromatosis and Iron Metabolism,
  Carlson J, Olsson S, eJIFCC vol 13 no 2, THE JOURNAL OF THE INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY.  Iron is easily removed from tissues through regular phlebotomy once a week until depleted iron stores are evident by S- ferritin < 30 µg/l. An early laboratory finding seen in HH is an abnormal saturation of transferrin (TS)to a level >45%.

• Hereditary hemochromatosis: a case study and review  Clin Lab Sci 2001 Summer Laboratory tests provide effective, inexpensive means of screening for and confirming hereditary hemochromatosis.

• Hereditary hemochromatosis.  Ann Clin Lab Sci. 1998 Sep-Oct   Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations.  Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.

• Hereditary Hemochromatosis. A Public Health Perspective  “Early detection of iron overload disease represents a major chronic disease prevention opportunity. Detection and treatment (phlebotomy) of iron overload, early in the course of the illness, can substantially reduce the severity of symptoms,  organ damage, and death from associated chronic diseases.” David Satcher, MD, PhD Assistant Secretary for Health and U.S. Surgeon General,  This Public Health Perspective: Hereditary Hemochromatosis was a collaborative effort by the CDC's Office of Genetics and Disease Prevention and members of the Hemochromatosis team at the Division of Nutrition and Physical Activity at CDC's National Center for Chronic Disease Prevention and Health Promotion.  (April 2001)

• Hereditary Hemochromatosis 
  CME Activity, Release Date: 2/28/2000 Expiration Date: 2/28/2002 From the February 2000 Issue of Physician Assistant  Objectives: After reading the article, the reader should be able to:
  1. describe the pathophysiology of hereditary hemochromatosis;
  2. recognize the clinical symptoms and signs of hereditary hemochromatosis;
  3. outline screening and evaluation testing; and
  4. provide accurate diagnosis, management, and treatment.

• Hereditary Hemochromatosis FamilyPractice.com  Robert B. Hash, MD, Department of Family Medicine, Mercer University School of Medicine, Macon, Ga. [J Am Board Fam Pract Dec. 2000] Considering the prevalence of the disease, it is important for physicians to consider it in the differential diagnosis when patients complain of the common signs and symptoms. For most patients hereditary hemochromatosis can be successfully treated in the physician's office. Early diagnosis and treatment, before signs of iron toxicity, if possible, can result in improved quality and quantity of life for many patients.

• Hereditary hemochromatosis: diagnosis and treatment in primary care Tenn Med 1999 Nov With early detection and treatment this can be a manageable chronic disease. If undetected, it is potentially fatal.

• Hereditary hemochromatosis: impact of molecular and iron-based testing on the diagnosis, treatment, and prevention of a common, chronic disease.  Arch Pathol Lab Med. 1999 Nov Press RD. Department of Pathology, Oregon Health Sciences University, Portland 97201, USA. pressr@ohsu.edu This direct HFE mutation test can now be used not only to confirm the diagnosis of HH in those with symptomatic disease, but also, perhaps more importantly, to detect those with presymptomatic iron overload in whom future disease manifestations may be prevented (with phlebotomy therapy).

• Hereditary hemochromatosis in children, adolescents, and young adults.  Am J Pediatr Hematol Oncol. 1988 Spring  Young individuals who should be screened for iron overload include patients with cardiac myopathies, hypogonadism, amenorrhea, loss of libido, diabetes mellitus, other endocrine disorders, cirrhosis of the liver, and arthritis, as well as the siblings, parents, and children of patients with hereditary hemochromatosis or iron loading of unknown cause.

• Hereditary hemochromatosis  
  J Fam Pract, 44(3):304-8 1997 Mar  Hereditary hemochromatosis is a genetic disorder of iron metabolism that has an excellent prognosis if diagnosed early.

• Hereditary hemochromatosis masquerading as rheumatoid arthritis
  Early erroneous diagnosis of rheumatic disease is common in subjects with arthropathy due to hereditary hemochromatosis Ann Ital Med Int 2001 Jan-Mar

• Hereditary hemochromatosis: presentation and diagnosis in the 1990s. 
  Am J Gastroenterol. 1997 May Bacon BR, Sadiq SA. With the use of screening iron studies on routine serum chemistry panels, patients with hemochromatosis can be identified and subsequently treated before they have symptoms or organ damage.

• Hereditary hemochromatosis: Preventing chronic effects of this underdiagnosed disorder
  Sharon M. McDonnell, MD, MPH; David Witte, MD, PhD VOL 102 / NO 6 / DECEMBER 1997 / POSTGRADUATE MEDICINE.  In this article, Drs McDonnell and Witte discuss the diagnosis and management of this underrecognized problem as well as the various issues involved in screening. An illustrative case of hemochromatosis is also included.

• Hereditary hemochromatosis Rev Med Interne 2000 Nov  At present, any patient admitted with an isolated case of asthenia, or with arthralgia or hypertransaminasemia should be examined via transferrin-saturation testing: if the transferrin saturation coefficient is > 45%, then the presence of the C282Y mutation should be investigated to confirm the diagnosis of hemochromatosis. A liver biopsy is no longer necessary to establish the diagnosis.

• Hereditary haemochromatosis should be more widely known about
   LETTERS on BMJ by William Rosenberg, Martin Howell, Paul Roderick, Diana Eccles, and Ian Day BMJ 1999 in response to Haemochromatosis and exercise related joint pains.

• Hereditary Hemochromatosis Since Discovery of the HFE Gene  Clinical Chemistry 2001 [a pdf file] Includes an algorithm for screening and diagnosis of hemochromatosis. This review provides a comprehensive discussion of known mutations in the HFE gene and their phenotypic expression.

• HFE mutations, iron deficiency and overload in 10,500 blood donors. 
  Br J Haematol 2001 Aug People with genetic haemochromatosis (GH) accumulate iron from excessive dietary absorption. In populations of northern European origin, over 90% of patients are homozygous for the C282Y mutation of the HFE gene.

• HFE-PROTEIN IN HEREDITARY HEMOCHROMATOSIS
  Hereditary hemochromatosis is the most common known autosomal recessive disorder in Caucasians

• High incidence of blood disease in Irish babies  
  Irish Medical Times April 14, 2000 Routine genetic testing of newborn babies may be warranted because of the high incidence of a serious blood disease in the Irish population. Dr John Crowe, gastroenterologist at the Centre for Liver Disease, Mater Hospital said that one in 86 Irish babies are genetically predisposed to haemachromatosis, which is the highest incidence in the world.

• Homozygosity for hemochromatosis: clinical manifestations.  Ann Intern Med. 1980 Oct; Diagnosis of asymptomatic hemochromatosis is important because organ damage may be prevented by early therapy.

• Inherited iron overload.  
  Acta Paediatr Scand Suppl. 1989 Several inherited forms of iron overload have been described. It is now accepted that HC, usually regarded as a disease of adult life, is an inherited disorder, hence all first degree relatives must be presumed to be at increased risk of developing iron overload and the diagnosis is now frequently made in young relatives. The combination of serum iron, transferrin saturation and serum ferritin determination will detect iron overload in an early, precirrhotic stage

• Interpretation of iron studies in adolescent haemochromatosis Clin Lab Haematol 1999 Apr;21(2):129-31 This case highlights that a low serum ferritin does not exclude the diagnosis of HH and that the availability of genetic testing can now enable probands and affected family members to be identified.

• Investigating Anaemia and Iron Storage Disease
  Discussion of the different types of anemia, as well as the effects of iron overload.  

• Iron and colorectal cancer risk: human studies  Nutr Rev 2001 May Because iron is broadly supplemented in the American diet, the benefits of iron supplementation need to be measured against the long-term risks of increased iron exposure, one of which may be increased risk of colorectal cancer.

• Iron catalyzed oxidative damage, in spite of normal ferritin and transferrin saturation levels and its possible role in Werner's syndrome, Parkinson's disease, cancer, gout, rheumatoid arthritis, etc. Med Hypotheses 2000 Sep the disease is often overlooked by physicians, until several organs have been damaged permanently (heart, liver, brain, pancreas, kidneys, spleen, etc.). Moreover, since ferritin, transferrin saturation and hematocrit levels are not directly related to cellular iron levels, and since excess iron can wreak havoc in the cell, we can conclude that there is a need for a better way to evaluate intracellular iron levels and especially the intracellular free iron levels by a non-invasive technique.

• Iron is Hot:  An Update on the Pathophysiology of Hemochromatosis: Blood Journal Sept. 15, 1998  Genetic iron overload disorders are prevalent yet poorly understood. [A pdf file.]

• Iron Loading and Disease Surveillance
  Eugene D. Weinberg   Indiana University, Bloomington, Indiana   Emerging Infectious Diseases Journal, National Center for Infectious Diseases, Centers for Disease Control and Prevention. Excessive iron in specific tissues and cells (iron loading) promotes development of infection, neoplasia, cardiomyopathy, arthropathy, and various endocrine and possibly neurodegenerative disorders.

• Iron overload and public health
  Bull Acad Natl Med. 2000  Genetic hemochromatosis, due to its frequency (about 300,000 cases in France) and to its severity, must be considered as a public health burden. Its curability--insofar as its diagnosis has been made early--and the disposal of non invasive and reliable phenotypic (transferrin saturation) and genotypic (HFE C282Y mutation) tests make its diagnosis easy.

• Iron Overload Disease due to Hereditary Hemochromatosis  CDC website, National Center for Chronic Disease Prevention and Health Promotion.  Early detection and treatment for this genetic condition can lessen morbidity and mortality, and in some cases prevent the onset of disease. Therefore, early detection of hemochromatosis represents a major chronic disease prevention opportunity.

• Iron Overload Disorder Common and Increases Risk for Heart Attacks
  Full Health Nutrition Canada ArterialHealth e-News^© October 1999 A genetic defect that causes iron overload disease is the most common inherited disorder among whites, affecting one in 188 people of northern European descent.

• Iron Overload (Hemosiderosis; Hemochromatosis) The Merck Manual of Diagnosis and Therapy Section 11. Hematology And Oncology Chapter 128. Hemochromatosis is often diagnosed late in the course of disease after significant tissue injury is present because the clinical symptoms are insidious and the extent of organ involvement varies; thus, the full clinical picture evolves slowly

• Iron overload without the C282Y mutation in patients with epilepsy  J Neurol Neurosurg Psychiatry 2001 Apr  These results indicate that iron overload other than the C282Y mutation underlies epilepsy.

• Iron: 'Too Much Is A Problem' by Joseph B. Verrengia [News Science Writer]  High levels of iron, already considered to be a major risk factor in heart attacks, are being implicated in the progression of AIDS, Lou Gehrig's disease and cancer.   "Iron will be the cholesterol of the 1990s," McCord predicts, ". . .most people don't know their iron status."

• Is hemochromatosis a risk factor for Alzheimer’s disease?   Journal of Alzheimer's Disease Volume 3, Number 5, October 2001 Pages 471-477 J. R.Connor, E. A. Milward, S. Moalem, M. Sampietro, P. Boyer, M. E.Percy, C. Vergani, R. J. Scott, M. Chorney (communicated by Paolo Zatta)

• Is there a threshold of hepatic iron concentration that leads to cirrhosis in C282Y hemochromatosis? Am J Gastroenterol 2001 Feb  From this analysis, it appears that a hepatic iron concentration >283 micromol/g is associated with cirrhosis. However, the low sensitivity of this threshold suggests that other cofactors contribute to the development of cirrhosis in hemochromatosis. Early diagnosis is encouraged to initiate iron depletion before the development of cirrhosis.

• Long-term survival analysis in hereditary hemochromatosis.
  Gastroenterology. 1991 Aug Early diagnosis and treatment of hemochromatosis in the precirrhotic stage can lead to long-term survival similar to that in the general population. The presence of cirrhosis significantly increases mortality and is the major clinical factor affecting survival.

• Long-term survival in patients with hereditary hemochromatosis Gastroenterology, Vol 110, 1107-1119, 1996 by American Gastroenterological Association   Prognosis of hemochromatosis and most of its complications, including liver cancer, depend on the amount and duration of iron excess. Early diagnosis and therapy largely prevent the adverse consequences of iron overload. 

• Making a Difference in Genetic Disease 
  Endeavor  VOLUME ONE NUMBER TWO Ernest Buetler M.D.  It will be the largest such screening study ever undertaken. The NIH and the CDC have provided funding of more than $4,000,000 for these clinical studies and the basic studies of iron metabolism that will be performed in the Beutler laboratory. 

• Management of hereditary hemochromatosis. Blood Rev. 1994 Dec Phatak PD, Cappuccio JD. Early diagnosis and institution of phlebotomy treatments will prevent these manifestations and normalize life expectancy. Once organ damage is established many of the manifestations are irreversible. Since the early manifestations of the disease are subtle, a case can be made for routine screening.

• Management of hemochromatosis. Hemochromatosis Management Working Group.
  Ann Intern Med. 1998 Dec 1  Barton JC, McDonnell SM, Adams PC, Brissot P, Powell LW, Edwards CQ, Cook JD, Kowdley KV.  The complications of iron overload in hemochromatosis can be avoided by early diagnosis and appropriate management.

• Metabolic arthropathies 
  The clinical and radiologic presentations of the arthropathy of hemochromatosis have been extensively reviewed. Screening for the disease appears important, because it is the only way to prevent progressive worsening of organ involvement and arthropathy in particular. Curr Opin Rheumatol 1994 Jul.

• Mild liver enzyme abnormalities: eliminating hemochromatosis as cause. David L. Witte Clinical Chemistry. 1997;43:1535-1538 Laboratory-initiated screening programs using 
  unsaturated iron-binding capacity can eliminate symptomatic hemochromatosis. Detection of hemochromatosis
  before development of cirrhosis or diabetes followed by removal of iron by therapeutic phlebotomy is associated
  with length and quality of life identical to age-matched controls.

• Molecular genetics of hemochromatosis 
  Ann Endocrinol (Paris) 1999 Sep Hemochromatosis is a recessive disorder of iron metabolism characterized by progressive iron loading of parenchymal organs, which accounts for clinical complications such as cirrhosis, diabetes mellitus, cardiopathy, endocrine dysfunctions and arthropathy.

• Mutation analysis of the HFE gene in german hemochromatosis patients and controls using automated SSCP-based capillary electrophoresis and a new PCR-ELISA technique. Scand J Gastroenterol 2001

• Mutation screening for prenatal and presymptomatic diagnosis: cystic fibrosis and haemochromatosis Abstract. Eur J Pediatr 2000 Dec; Mutation analysis is widely recommended for presymptomatic diagnosis of cystic fibrosis and hereditary haemochromatosis because of the presumed benefit.Click here for full text pdf file.

• Nonexpressing homozygotes for C282Y hemochromatosis: minority or majority of cases?
  Mol Genet Metab. 2000 Sep-Oct In this review, the available data on nonexpressing C282Y homozygotes is collected including information on pathogenesis, environmental interactions, and implications for population screening using genetic testing

• Noninvasive Prediction of Fibrosis in C282Y Homozygous Hemochromatosis 
  GASTROENTEROLOGY 1998;115:929-936  In C282Y homozygous patients, the diagnosis of severe fibrosis relies on liver biopsy, but absence of severe fibrosis can be accurately predicted in most patients on the basis of simple clinical and biochemical variables.

• Nutrient overload at breakfast News You Can Use at US News.com  7/30/01 Your breakfast cereal may be giving you too much of a good thing.

• Overview on Iron Overload and Hemochromatosis CDC website, National Center for Chronic Disease Prevention and Health Promotion.  Early detection of hemochromatosis is essential because the disease’s potentially serious complications can be prevented by early therapy.

• Pathology Cases for Diagnosis: A 37 year old male is referred to the liver clinic for evaluation of abnormal liver related enzymes.  Includes pictures of biopsy slides. Case 96-19: Liver II Contributed by D. Robert Dufour, M.D., CAPT, MC, USNR-R Date Available: July 22, 1996 - December 31, 1996 

• Population screening in hereditary hemochromatosis   Annu Rev Public Health 2000

• Practice guideline development task force of the College of American Pathologists. Hereditary hemochromatosis. Witte DL, Crosby WH, Edwards CQ, Fairbanks VF, Mitros FA. College of American Pathologists Clin Chim Acta 1996 Feb. In view of the high prevalence in the American population (prevalence varies with ethnic background), the low cost of diagnosis and treatment, the efficacy of treatment if begun early, and, on the other hand, high costs and low success rate of late diagnosis and treatment, systematic screening for hemochromatosis is warranted for all persons over the age of 20.

• Preclinical hereditary hemochromatosis--is there an indication for preventive screening?
  Ugeskr Laeger. 1995 Jul 24  In preclinical hereditary haemochromatosis, early diagnosis and treatment is essential in order to prevent organ damage and to improve prognosis. Prophylactic screening is recommended.

• Prevalence of hereditary hemochromatosis among healthy workers.  Diagnostic value of transferrin saturation assay  An Med Interna. 2000 Dec An early diagnosis and proper management with frequent phlebotomies are known to improve life expectancy and quality of life. Diagnosis is suggested by an elevated Transferrin saturation (TS) (more than 60%).

• Prevalence of hereditary hemochromatosis in a Massachusetts corporation: is Celtic origin a risk factor?  Hepatology. 1997 Jun.  Two thousand two hundred ninety-four employees were screened, and 5 cases of HHC were detected.

• Prevalence of idiopathic hemochromatosis in Italy: study of 1301 blood donors. 
  Haematologica 1990 Jul-Aug  Large-scale screening of young adults based on TS and SF determinations should be proposed for early diagnosis and treatment.

• Preventing manifestations of hereditary haemochromatosis through population based screening. To evaluate the efficacy of identifying presymptomatic hereditary haemochromatosis through population based screening.  J Med Screen 1994 Jan

• Psychosocial impact of C282Y mutation testing for hemochromatosis
    Genet Test 2001 Summer

• Recognition and management of hereditary hemochromatosis.   Am Fam Physician 2002 Mar 1 65:853-60 Brandhagen DJ, Fairbanks VF, and Baldus W Mayo Medical School, Rochester, Minnesota, USA. The HFE gene test is useful in confirming the diagnosis of hereditary hemochromatosis, screening adult family members of patients with HFE mutations and resolving ambiguities concerning iron overload.

• Recognizing genetic hemochromatosis.  J La State Med Soc. 1994 Dec  This article reviews the disease process hemochromatosis, which is now recognized as one of the most common genetic disorders.  It is imperative that physicians learn to recognize early signs and symptoms of hemochromatosis so that treated patients can expect a normal life span with minimal medical intervention.

• Refractory heart failure in a 26-year-old woman with idiopathic hemochromatosis 
  Rev Port Cardiol. 1994 Oct  In this paper, we report a case of a young woman with a eight years evolution of amenorrhea, cardiac failure, diabetes mellitus and increased pigmentation of the skin, associated with biochemical markers of iron overload. It is emphasized that hemochromatosis most be excluded in all patients with a unexplained cardiac failure.

• Relation between iron stores and non-insulin dependent diabetes in men: case-control study 
  Non-insulin dependent diabetes mellitus is a common complication of diseases of iron overload such as haemochromatosis; 53-80% of patients with haemochromatosis develop diabetes. The development of diabetes in haemochromatosis is related to the magnitude of the excess iron. 1998, British Medical Journal BMJ 1998;317:727730 (12 September)

• Renal Transplantation and Evolution of Hemochromatosis:  A Clinical Case Report
  Despite being one of the world's most frequent autosomal recessive diseases, there are very few cases in the literature concerning hereditary hemochromatosis and renal transplantation. [a pdf file]

• Review article: the screening, diagnosis and optimal management of haemochromatosis.
  Aliment Pharmacol Ther. 1997 Aug   George DK, Powell LW.  Joint Liver Program, Queensland Institute of Medical Research, Brisbane, Australia.  Haemochromatosis is common, occurring in approximately 1 in 300 people in Caucasian populations, and untreated can cause serious morbidity and early death.

• Risk of disease in siblings of patients with hereditary hemochromatosis Digestion 2001

• Role of C282Y mutation in haemochromatosis gene in development of type 2 diabetes in healthy men: prospective cohort study. British Medical Journal BMJ 2000;320:17061707 (24 June) As the incidence of diabetes in northern Europe is among the highest in the world and rising, screening for C282Y mutation by DNA analysis, monitoring of iron status, and iron depleting treatment could potentially constitute new important measures in the primary prevention of diabetes.

• Screening for genetic haemochromatosis in a rheumatology clinic
  Aust N Z J Med 1994 Feb The increased prevalence of GH in this group of patients with peripheral arthropathy provides an excellent justification for the routine screening of patients with peripheral arthritis for the exclusion of iron overload

• Screening for genetic haemochromatosis in blood samples with raised alanine aminotransferase
  Gut 2000;46:707-710 ( May )
  
• Screening for hemochromatosis  At the present time, we believe that further data regarding both the exact disease burden and the outcomes of screening studies particularly in the general community are required before widespread population screening is introduced. Clin Chim Acta 2002 Jan
  
• Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons Scand J Gastroenterol 2001 Oct
  
• Screening for Hereditary Hemochromatosis in Siblings and Children of Affected Patients
  A Cost-Effectiveness Analysis Hashem B. El-Serag, MD, MPH; John M. Inadomi, MD; and Kris V. Kowdley, MD Annals of Internal Medicine, 15 February 2000 Volume 132 Number 4. 
  HFE gene testing for the C282Y mutation is a cost-effective method of screening relatives of patients with hereditary hemochromatosis.
  
• Screening for hereditary haemochromatosis should be implemented now.  
  BMJ 2000;320:183 ( 15 January ) We believe that to benefit all those at risk there is an ethical imperative to implement screening for the major mutation causing haemochromatosis now, rather than wait years for confirmation of what is currently known that at least half of those with the predisposing genotype will develop some form of the disease.
  
• Screening for Iron Overload due to Hereditary Hemochromatosis 
  CDC website, Reyes, Michele, PhD and Muin J. Khoury, MD, PhD,  National Center for Chronic Disease Prevention and Health Promotion  Identifying people early with evidence of iron overload represents a major chronic disease prevention opportunity.

• Screening Newborns for Genetic Disease Helps Parents By Anne Harding NEW YORK (Reuters Health) -Dec. 7, 2000  Screening newborns for hemochromatosis is effective, practical, and can save their parents' lives, according to French researchers who have developed a program for identifying infants with this common and potentially fatal genetic disease.  [no longer available online]

• Should all patients with diabetes mellitus be screened for hemochromatosis?   Department of Family Medicine University of California, Los Angeles 924 Westwood Blvd, Suite 650 Los Angeles, CA 90095-1628  West J Med 2002;176:110-114  Enhanced case finding becomes the first stage in a public health response when evidence has emerged for an effective early treatment of a disorder. It means the detection of HHC at the time of early symptoms, and it allows patients to benefit from early phlebotomy.  The implementation of this approach would include adding fasting serum transferrin saturation to the usual workup of patients with newly diagnosed diabetes mellitus, arthritis, and impotence.  The CDC recommends such iron-overload testing in anyone with possible symptoms of hemochromatosis, which includes patients with newly diagnosed diabetes mellitus.
  
• Should asymptomatic haemochromatosis be treated?  BMJ 2000;321:955 ( 14 October ) Letters to BMJ on these topics: 
      Alternative strategies to appropriate diagnosis need testing
      Consequences of screening must be made known
      Update from Seamark and Hutchinson
  
• Should iron preparations be available only by prescription?  Tidsskr Nor Laegeforen 2001 Feb 10 No one should use iron tablets until iron deficiency and its cause has been ascertained. 

• Should we genetically test everyone for haemochromatosis?
   J Med Ethics. 1999 Apr  This paper will identify and discuss key issues regarding DNA-based population screening for haemochromatosis, and argue that population-based genetic screening for haemochromatosis should be supported when a number of contentious issues are addressed
• Study aims to create consensus on iron overload test  A Kaiser Permanente unit and four other centers will split $30 million to assess who needs to be screened for the common defect  Wednesday, June 27, 2001. By Oz Hopkins Koglin of The Oregonian staff.   Comments by Sandra Thomas, AHS.
• The articular damage of hemochromatosis. A little known aspect Recenti Prog Med 1999 Apr The aim of this report is to underline that the patients with premature osteoarthritis or unexplained chondrocalcinosis must be screened for genetic haemochromatosis in order to formulate the correct diagnosis before the development of severe internal organ involvement
• The challenge of integrating genetic medicine into primary care.  
  BMJ. 2001 Apr 28 Population screening for hereditary haemochromatosis has been promoted because of the relatively high prevalence of mutations in the HFE gene that cause the disease and because there is effective treatment through regular phlebotomy.
• The diagnosis of hemochromatosis in the era of the gene Ann Endocrinol (Paris). 1999 Sep [article in French] 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.
  
• The effect of HFE mutations on serum ferritin and transferrin saturation in the Jersey population Br J Haematol 1998 May
• The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis. Hepatology. 1997 Jan The nonspecific nature of the presenting features in patients and the presence of significant clinical symptoms in patients discovered through family investigations underscore the importance of family and population screening for hemochromatosis.
• The significance of haemochromatosis gene mutations in the general population: implications for screening.  Gut. 1998 Dec HFE mutations are present in 38.4% of the population, affect serum iron indexes, and are important determinants of iron status. The population frequency of genetically defined haemochromatosis (C282Y homozygosity) is approximately one in 200 and is higher than the prevalence of clinically apparent haemochromatosis
  
• Too much iron can be dangerous By Andreas von Bubnoff  Staff Writer New University Newspaper. According to Gordon McLaren, this hemochromatosis study is the first trial of large-scale genetic screening, at least in adults. Thus, results of the study may also have an impact on future legislation regulating genetic screening, he said. "The problem is the disease is silent until something goes wrong," Gordon McLaren said. "So you need to be checking people [for the disease] before they have any problems."
  
• Update on hereditary hemochromatosis and the HFE gene. Brandhagen DJ, Fairbanks VF, Batts KP, Thibodeau SN. Division of Gastroenterology and Hepatology and Internal Medicine, Mayo Clinic Rochester, Minn 55905, USA. Mayo Clin Proc 1999 Sep
  
• Use of HFE Mutation Analysis for Hereditary Hemochromatosis:  The Need for Physician Education in the Translation of Basic Science to Clinical Practice
  Manish Kohli, MB, ChB, Steven A. Schichman, MD, PhD, Louis Fink, MD, Clive S. Zent, MB, BCh, Department of Internal Medicine, Division of Hematology/Oncology and the Department of Pathology, John L. McClellan Memorial Veteran's Hospital and University of Arkansas for Medical Sciences, Little Rock.  Southern Medical Journal
  
• What's new in hemochromatosis.  Curr Opin Hematol 2001 Mar  The high correlation of HFE to HHC has caused it to be considered as a candidate gene for population-based genetic testing for diagnosis and detection of predisposition to HHC. 
• Will Your Genes Prevent You From Getting Health Insurance? St. Louis University News Release  October 13, 2000 "People may be reluctant to take advantage of genetic tests that could save their lives," Dr. Bacon said. "In hemochromatosis, for example, symptoms usually do not appear until between 40 and 60 years of age. By then, the patient may have already sustained serious liver damage. Early detection is essential. No one should be afraid to seek information to make educated choices regarding their health."

Click on this link to read about HH. Discussion of a liver biopsy is also here: 

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