Hemochromatosis

Question 1

characterized by increased intestinal iron absorption that results from low expression of the iron-regulatory protein hepcidin.

Answer 1

Hemochromatosis

The most common form of HH by far is HFE-related HH.

in all types of HH, iron overload results from impairment in the hepcidin regulatory pathway.

Question 2

Loss-of-function mutations decrease the cell surface localization of ferroportin, thereby reducing its ability to export iron.

Answer 2

This disorder is sometimes termed classical ferroportin disease and differs from the other forms of HH; unlike other forms of HH, the hepatic iron loading is primarily in Kupffer cells, rather than hepatocytes.

Question 3

is observed primarily in sub-Saharan Africa and is considered to be the result of a non–HFE-related genetic susceptibility to excessive dietary iron intake.

Answer 3

African iron overload (Bantu siderosis)

Question 4

an iron-regulatory hormone that plays a central role in iron homeostasis by coordinating iron absorption, mobilization, and storage to meet the iron requirements of erythropoiesis and other iron-dependent processes

Answer 4

Hepcidin

Question 5

The resulting hypoferremia

Answer 5

plays a major causal role in the anemia of chronic disease

Question 6

Many patients with HFE-related HH

Answer 6

homozygous relatives of probands during family screening studies or by the results of serum iron studies in routine screening blood chemistry panels

Question 7

HFE-related HH

Answer 7

symptomatic HFE-related HH are 40 to 50 years of age at the time of detection.

Question 8

HFE-related HH

Answer 8

the most common are weakness and lethargy, arthralgias, abdominal pain, and loss of libido or potency in men.

Patients with HFE-related HH may have nonspecific RUQ abdominal pain that is most likely caused by hepatic capsular distention.

Hepatomegaly is found on physical examination in a majority of patients; splenomegaly and other complications of chronic liver disease, including ascites, edema, and jaundice, may be present.

Question 9

Many commercial laboratories added iron and total iron-binding capacity (TIBC)

Answer 9

TS calculated as iron ÷ TIBC × 100%, to their panel of screening serum chemistry tests, and in many patients, a TS was obtained inadvertently even though the test had not been specifically ordered.

Question 10

the serum ferritin value is higher than 1000 ng/mL or liver enzymes are elevated,

Answer 10

liver biopsy is indicated.

When a liver biopsy specimen is obtained, Perls’ Prussian blue stain is used for the determination and localization of storage iron.

Question 11

The treatment of HFE-related HH

Answer 11

relatively straightforward; most patients can be treated with routine therapeutic phlebotomy

Each unit of whole blood (500 mL) contains approximately 200 to 250 mg of iron, depending on the hemoglobin concentration; therefore, C282Y homozygotes who have 10 to 20 g of excess storage iron require extended phlebotomy regimens (40 to 80 units of blood removed).

Question 12

The iron-chelating drug deferoxamine is used in patients with HFE-related HH and cardiac manifestations or in patients who cannot tolerate phlebotomy.

Answer 12

Deferoxamine, 20 to 50 mg/kg/day, is administered 5 days per week as a continuous subcutaneous infusion (over a 12-hour period each day) via a portable pump.

Deferasirox (Exjade), a once-daily oral iron chelator, appears to be effective in the treatment of HH