Iron Disorder Overload Disease

Aceruloplasminemia and atransferrinemia are rare iron overload diseases. Both diseases are caused by hereditary autosomal recessive disorders. This means that aceruloplasminemia and atransferrinemia occur only when the genetic mutations that cause the iron overload diseases are inherited from both parents. People who inherit the mutations from only one parent are carriers, but do not develop the disease themselves.

Aceruloplasminemia and Ceruloplasmin

Aceruloplasminemia is an iron overload disease caused by mutations in the ceruloplasmin gene. Ceruloplasmin is a copper containing plasma protein that removes excess iron from cells. The mutations in the ceruloplasmin gene cause a lack of ceruloplasmin in the blood of people with aceruloplasminemia, or may cause variant types of ceruloplasmin that do not function correctly.

Due to insufficient ceruloplasmin, aceruloplasminemia leads to iron overload in the pancreas, the liver, the retina and the brain. Complications of aceruloplasminemia can be serious, and include:

  • abnormal gait (similar to the characteristic gait of Parkinson’s disease)
  • dementia
  • diabetes
  • neurologic degeneration
  • retinal damage
  • tremors.

Like many genetic iron overload diseases, aceruloplasminemia can be asymptomatic for years: symptoms usually do not become apparent until adulthood. The effects of ceruloplasmin insufficiency tend to develop between thirty and fifty years of age.

Aceruloplasminemia Treatment

Aceruloplasminemia is a rare iron overload disease and, as such, few treatment options exist. Evidence is inconclusive, but intense chelation therapy appears to slow the progression of aceruloplasminemia.

Chelation therapy is used to treat several iron overload diseases: the treatment uses selected body proteins and chemicals that bind to iron molecules in the blood. These substances and the attached iron are then excreted through urine and fecal matter.

Aceruloplasminemia was once called hereditary ceruloplasmin deficiency.

Atransferrinemia and Transferrin

Like aceruloplasminemia, atransferrinemia is one of the autosomal recessive iron overload diseases, meaning the genetic mutation for atransferrinemia must be inherited from both parents.

The genetic mutation that causes atransferrinemia (also called hypotransferrinemia) affects transferrin levels. Transferrin is a plasma protein that transports iron through the blood and delivers iron to the liver, spleen and bone marrow. Atransferrinemia results from an absence of transferrin.

Atransferrinemia Complications

Although iron overload appears to be the opposite of anemia, atransferrinemia simultaneously causes iron overload and anemia. The lack of transferrin prevents bone marrow from receiving sufficient iron to make red blood cells in adequate amounts. Those red blood cells that are produced are smaller than healthy red blood cells, and pale in color.

While insufficient transferrin causes anemia, atransferrinemia also causes iron overload in the heart and liver: iron that cannot be used to make red blood cells and hemoglobin accumulates in these organs. Left untreated, atransferrinemia can cause organ damage and heart failure.

Atransferrinemia Treatment and Transferrin Infusions

Plasma infusions of transferrin are the standard treatment for atransferrinemia. Regular transferrin infusions maintain proper levels of the protein in the blood, preventing both anemia and iron overload. Transferrin infusions must be maintained for life to prevent a recurrence of iron overload.

Resources

Andrews, N. C. (1999, December 23). Disorders of iron metabolism. The New England Journal of Medicine 341(26), 1986-1995.

Beers, M. H.,