Aceruloplasminemia

Aceruloplasminemia is a disorder in which iron gradually accumulates in the brain and other organs. Iron accumulation in the brain results in neurological problems that generally appear in adulthood and worsen over time.

People with aceruloplasminemia develop a variety of movement problems. They may experience involuntary movements such as rhythmic shaking (tremors), jerking movements (chorea), eyelid twitching (blepharospasm), and grimacing. They may also have difficulties with coordination (ataxia). Some affected individuals develop psychiatric problems and progressive deterioration of cognitive functions (dementia) in their forties or fifties.

In addition to neurological problems, iron accumulation in the tissues and organs results in a corresponding iron deficiency in the blood, leading to a shortage of red blood cells (anemia). Affected individuals may also have diabetes mellitus caused by iron damage to certain cells in the pancreas. These cells make insulin, which is a hormone that helps control blood sugar levels. Anemia and diabetes usually occur by the time an affected person is in his or her twenties. Affected individuals also have changes in the light-sensitive tissue at the back of the eye (retina). The changes result in small opaque spots and areas of tissue degeneration (atrophy) around the edges of the retina. These abnormalities usually do not affect vision but can be observed during an eye examination.

Aceruloplasminemia has been seen worldwide, but its overall prevalence is unknown. Studies in Japan have estimated that approximately 1 in 100,000 individuals in this population are affected.

Mutations in the CP gene cause aceruloplasminemia. The CP gene provides instructions for making a protein called ceruloplasmin, which is involved in iron transport and processing. Ceruloplasmin helps move iron from the organs and tissues of the body and prepares it for incorporation into a molecule called transferrin, which transports it to red blood cells.

CP gene mutations result in the production of ceruloplasmin protein that is unstable or nonfunctional, or prevent the protein from being secreted by the cells in which it is made. When ceruloplasmin is unavailable, the resulting iron transport problems lead to iron accumulation, neurological dysfunction, and the other health problems seen in aceruloplasminemia.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.