Aceruloplasminemia is a rare autosomal recessive disorder in which the liver cannot synthesis the protein ceruloplasmin.
It is caused by a mutation with a five-base pair insertion in exon 7 in the CP gene, which provides for making the protein called ceruloplasmin.
The CP gene mutation results in the production of ceruloplasmin protein that is unstable or nonfunctional.
Ceruloplasmin is involved in iron transport and processing.
Ceruloplasmin is needed to transport copper around the blood, and with decreased synthesis results in copper deficiency in the brain, with neurological problems that generally appear in adulthood and worsen over time.
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 to help carry oxygen.
In the absence of ceruloplasmin, ferroxidase does not convert ferrous iron to ferric iron, and iron deposition occurs in various organs.
The classic triad of clinical findings includes neurologic dysfunction, retinal degeneration, and diabetes due to iron deposition in the brain, retina, and pancreas.
Prevalence is unknown, but in Japan it is estimated that approximately 1 in 2 million adults in this population are affected.
It is a neurodegenerative disorder with brain iron accumulation
Patients with aceruloplasminemia may experience dystonia of the head and neck, resulting in repetitive movements and contortions.
Neurologic symptoms include dementia, other neuropsychiatric findings and motor symptoms.
Patients with homozygous mutations, making up 85% of patients, the first neurologic symptoms often is cognitive impairment.
Involuntary movements may also occur, such as tremors, chorea, blepharospasms, grimacing, ataxia, and the lack of coordination of muscle movements.
Some develop psychiatric problems and midlife dementia.
The type of neurological disruption is related to regions of iron deposition in the brain and liver.
The first sign of disease is often diabetes, followed by microcytic anemia with low serum iron levels and elevated ferritin levels.
Diabetes mellitus caused by iron damage to cells in the pancreas.
Iron deficiency anemia and diabetes usually occur by the time an affected person is in his or her twenties.
Retinal degeneration caused by excess iron is seen, with spots and areas of atrophy around the edges of the retina.
When ceruloplasmin is unavailable, transport of iron out of tissues is impaired, resulting in iron accumulation damage to cells in those tissues.
Diagnosis: blood tests demonstrating the absence of serum ceruloplasmin, combined with low serum copper concentration, low serum iron concentration, high serum ferritin concentration, or increased hepatic iron concentration.
Brain MRI scans can confirm diagnosis, demonstrating abnormal low intensity changes of iron accumulation in the brain.
Children of affected individuals are obligate carriers for aceruloplasminemia.
Prenatal testing for the CP gene is recommended if there is an identified relative with the disorder.
Siblings of those affected are at a 25% rate of of aceruloplasminemia.
In asymptomatic siblings, serum concentrations of hemoglobin and hemoglobin A1c should be monitored.
Involved patients should be monitored for glucose tolerance beginning in early teen years to evaluate the onset of diabetes mellitus.
Patients at risk should avoid taking iron supplements.
Treatment includes the use of iron chelating agents to lower brain and liver iron stores, and to prevent progression of neurologic symptoms.
Repetitive use of FFP can even improve neurologic symptoms.
Antioxidants such as vitamin E can be used to prevent tissue damage to the liver and pancreas.