|Hereditary or Idiopathic Hemochromatosis
Dambro: Griffith's 5-Minute Clinical Consult, 1999 - Robert A. Marlow MD,
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
Amenorrhea (22%), Dyspnea on exertion (15%), Neurologic symptoms (6%),
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)
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
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
Pancreatic enlargement, Cardiomegaly, Joint deposition of iron
Excess hemosiderin in liver, pancreas, myocardium, thyroid, parathyroid,
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
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
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
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)
Powell LW, Georg K, McDonnel SM, Kowdley KV. Diagnosis of hemochromatosis.
Ann Intern Med. 1998;129:925-31.
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.
Barany P, Eriksson LC, Hultcrantz R, Pettersson E, Bergstrom J. Serum
ferritin and tissue iron in anemic dialysis patient. Min Electrolyte Metab.
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.
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.
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 )
of Hemochromatosis (Annals of Internal Medicine, 1 December 1998.
129:925-931. Lawrie W. Powell)