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Hereditary or Idiopathic Hemochromatosis                                                                  

Dambro: Griffith's 5-Minute Clinical Consult, 1999 - Robert A. Marlow MD, MA

A hereditary disorder in which the small intestine absorbs excessive iron, & excess iron deposit in liver, pancreas, heart, joint, etc. Over the years, the involved organs begin to fail.   Predominant age: Present from birth, but symptoms usually present in the fifth and sixth decades.  Alcohol increases the absorption of iron (as high as 41% of patients with symptomatic disease are alcoholic). Other secondary causes of iron overload include multiple transfusion, oral iron excessive intake. 

Weakness (83%), Abdominal pain (58%), Arthralgia (43%), Loss of libido or potency (38%)
Amenorrhea (22%), Dyspnea on exertion (15%), Neurologic symptoms (6%), Hepatomegaly (83%)
Increased skin pigmentation (75%), Loss of body hair (20%), Splenomegaly (13%), Peripheral edema (12%)
Jaundice (10%), Gynecomastia (8%), Ascites (6%), Testicular atrophy, Hepatic tenderness, Diabetes mellitus symptoms

Repeated transfusions , Hereditary anemias with ineffective erythropoiesis ,  Alcoholic cirrhosis
Porphyria cutanea tarda, Atransferrinemia, Excessive ingestion of iron (rare)

Diagnostic Lab:

  • Transferrin saturation (serum iron concentration divided by total iron-binding capacity × 100): greater than 70% is virtually diagnostic of iron overload; 50% or higher warrants further evaluation
  • Serum ferritin: greater than 300 µg/L for men and 120 µg/L for women
  • Liver biopsy for stainable iron is the standard for diagnosis.
  • The prevalence of the C282Y-homozygous genotype ranges from 93 to 100% in well-defined pedigrees, and from 64 to 83% in nonfamilial studies; accordingly, the presence of the homozygous genotype provides very strong supportive evidence for the diagnosis of Hereditary Hemochromatosis. While virtually 100% of patients homozygous for C282Y will have elevated transferrin saturation (greater than 45%), and serum ferritin, a significant minority (up to 15%) may have an HII of less than 1.9, even though their HIC is above the upper limit of normal


  • Increased hepatic parenchymal iron stores, Hepatic fibrosis and cirrhosis with hepatomegaly
  • Pancreatic enlargement,  Cardiomegaly,  Joint deposition of iron
  • Excess hemosiderin in liver, pancreas, myocardium, thyroid, parathyroid, joints, skin


  • Removal of excess iron by repeated phlebotomy once or twice weekly to establish and maintain a mild anemia (hematocrit of 37-39%).  When the patient finally becomes iron deficient, a lifelong maintenance program of 4-6 phlebotomies a year to keep storage iron normal
  • Only when phlebotomy is not feasible or in the presence of severe heart disease should the iron-chelating agent deferoxamine (Desferal) be considered.

Annals of Internal Medicine - LETTER

Diagnosis of Hemochromatosis (Annals of Internal Medicine, 17 August 1999. )

To the Editor:
We take issue with the hemochromatosis laboratory criteria by Powell and colleagues (1). The authors concluded that

  • a serum transferrin saturation greater than 45%,
  • a serum ferritin level greater than 200 µg/L in premenopausal women, and
  • a serum ferritin level greater than 300 µg/L in men and postmenopausal women

are indicators for primary iron overload. Although the authors explain that elevated serum ferritin levels may be due to inflammation, infection, or cancer and suggest that acute-phase reactants be obtained to exclude these entities, they ignore the fact that in patients with end-stage renal disease (ESRD), the relation between tissue iron stores and serum ferritin levels is altered.

A relative increase in serum ferritin levels unrelated to iron stores or acute phase reactants is frequently observed (2, 3). Serum ferritin levels of 1000 µg/L or greater in patients with ESRD are not uncommon, and iron overload is extremely rare (3, 4). In one of our dialysis units, the mean serum ferritin level is 630 µg/L, with a median value of 601 (SD, 358 µg/L). By using bone marrow iron stores, we showed that a serum ferritin level less than 200 µg/L is highly specific for iron deficiency in patients with ESRD (2). Moreover, serum ferritin levels as high as 1200 µg/L may still be consistent with low to normal iron stores in patients with ESRD.

In a study on nutritional assessment (5), we showed that severely malnourished patients undergoing dialysis had the highest serum ferritin levels, and well-nourished patients undergoing dialysis had lower values. We also found an inverse correlation between serum ferritin and transferrin levels (r = -0.61) in patients with ESRD and showed that low serum transferrin levels due to malnutrition may cause an erroneously normal to high transferrin saturation ratio, even in the presence of iron deficiency (2, 5). We suggest that the hemochromatosis criteria be modified for patients with ESRD.

Kamyar Kalantar-Zadeh, MD, MP (University of California, San Francisco)
Friedrich C. Luft, MD (Humboldt University of Berlin, Germany) 


  1. Powell LW, Georg K, McDonnel SM, Kowdley KV. Diagnosis of hemochromatosis. Ann Intern Med. 1998;129:925-31.
  2. Kalantar-Zadeh K, Wünsch PH, Fink H, Höffken B, Kleiner M, Luft FC. Diagnosis of iron deficiency anemia in renal failure patients during post erythropoietin era. Am J Kid Dis. 1995;26:292-9.
  3. Barany P, Eriksson LC, Hultcrantz R, Pettersson E, Bergstrom J. Serum ferritin and tissue iron in anemic dialysis patient. Min Electrolyte Metab. 1997;23:273-6.
  4. NKF-DOQI clinical practice guidelines for the treatment of anemia of chronic renal failure. National Kidney Foundation-Dialysis Outcomes Quality Initiative. Am J Kid Dis. 1997;30(4 Suppl 3):S192-240.
  5. Kalantar-Zadeh K, Kleiner M, Dunne E, Nelson M, Ahern K, Koslowe R, et al. Total iron binding capacity-estimated transferrin concentrations in dialysis patients correlate with the subjective global assessment of nutrition. Am J Kid Dis. 1998;31:263-72.

In response:
Our discussion of the laboratory criteria for hemochromatosis was clearly in the context of an otherwise healthy person or one with clinical features suggestive of the disease. We stated that in this situation "the serum ferritin level defines the point at which hemochromatosis is expressing iron overload and treatment should be initiated." It is then that the serum ferritin level exquisitely reflects body iron stores. Other conditions can indeed cause an elevation in serum ferritin level out of proportion to iron stores, and we listed inflammation, infection, and cancer because they can complicate hemochromatosis. Renal disease is rare in hemochromatosis, and end-stage renal disease would be entirely unrelated. It is also noteworthy that most studies of chronic renal disease assess body iron stores by bone marrow iron. This is not applicable to hemochromatosis, in which hepatic iron concentration is increased while bone marrow iron stores are normal.

Lawrie W. Powell, MD, Ph, D. Keith George, MBChB, MRC
The Queensland Institute of Medical Research, Brisbane, Australia

Sharon McDonnell, MD ( Centers for Disease Control and Prevention Atlanta, GA 30333 )

Diagnosis of Hemochromatosis (Annals of Internal Medicine, 1 December 1998. 129:925-931. Lawrie W. Powell)