Author: Benedetta Maria Motta
Date: 24/12/2009



The Aceruloplasminemia is an autosomal recessive hereditary disease of iron metabolism in the absence of Ceruloplasmin due to mutations in the ceruloplasmin gene, without alteration of copper metabolism. This leads to an accumulation of iron in the pancreas, liver and brain. In relation to the sites of iron overload, the aCP is characterized by the classic triad: diabetes, retinal degeneration and neurological manifestations.
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),
  • grimacing.

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 and 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.

The Diseases DatabaseURL


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.
Miyajima H., Takahashi Y, Kono S. Aceruloplasminemia, an inherited disorder of iron metabolism. Biometals 2003;16:205-13

The age of onset of the disease is highly variable: the onset can occur in young or elderly, with mean of 51 years.


The symptoms, in order of frequency, are: retinal degeneration (93%), diabetes mellitus (89%), anemia (80%), neurological symptoms (73%) and cognitive decline and dementia (25%). There is no correlation between the degree of iron overload and duration with neurological symptoms and the clinical severity. Retinal degeneration is manifested by yellowish opacity and retinal pigment epithelium atrophy. Visual acuity is not impaired. Diabetes mellitus is secondary to the accumulation of iron which causes an increase in free radicals with toxic effects on cells producing insulin. Iron overload in the liver usually has no symptoms and there were no cases of liver cirrhosis.

Myiajima H. Aceruloplasminemia, an iron metabolic disorder. Neuropathology 2003;23(4):345-50
Deugnier Y, Turlin B.. Pathology of hepatic overload. World J. Gastroent. 2007;13(35):4755-60
McNeill A., Pandolfo M, Kuhn J. et Alii. The neurological presentation of ceruloplasmin gene mutations. Eur. Neurol. 2008;60:200-05


The diagnosis of Aceruloplasminemia, suspected for neurological disorders associated with diabetes and retinal degeneration and biochemical profile characterized by high ferritin with microcytic anemia, is confirmed by the lack of ceruloplasmin in serum (for analysis of serum is used antibodies to human ceruloplasmin ) with normal levels of copper in serum and urine and by DNA analysis. MRI is able to assess the accumulation of iron in liver, pancreas and brain and the brain abnormalities. Desossiglucosio-PET can highlight a hypometabolism of the basal ganglia. The neurological examination may reveal nystagmus, dysarthria, intention tremors and involuntary movements of limbs.


Aceruloplasminemia is caused by mutations in the gene encoding ceruloplasmin. 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. Excess iron functions as a powerful catalyst for organic oxidation. The iron-mediated free radicals cause oxidative stress that is the primary process of cellular toxicity that causes neuronal damage in brain regions involved.


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


Aggressive treatment with deferoxamine, a chelating agent that takes up iron, may halt the progression of these complications and, if started early, can prevent the accumulation of brain iron and neurological degeneration, while in advanced stages of disease, this therapy is ineffective. In some cases it has been attempted based therapy of zinc sulphate because metallotionin, macromolecule that binds the metal plays an important role in protecting the nervous system from free radical damage mediated by iron and its synthesis is induced by zinc supplement. However, the efficacy of this treatment is yet to be confirmed.

AddThis Social Bookmark Button