nbia-logo1

English French German Italian Spanish
Text Size

Aceruloplasminemia

Aceruloplasminemia is a form of NBIA characterized by iron accumulation, but there’s a twist. The iron collects not just in the brain, but in other organs, including the liver.

The disorder has mainly been studied in Japan, where it occurs in about one in 2 million adults. It is unclear how often it occurs in other populations. The gene responsible is CP, which encodes ceruloplasmin.

The main symptoms are retinal degeneration, diabetes and neurologic disease related to iron build-up in the basal ganglia. Movement problems include face and neck dystonia (involuntary muscle contractions, with repetitive movements or painful postures), blepharospasm (eyelid spasms), tremors and jerky movements.

Clinical Diagnosis

Individuals with aceruloplasminemia often present to doctors with anemia prior to onset of diabetes mellitus or neurologic symptoms. Physical traits, known as phenotypic expression, vary, even within families.

Physicians may do an MRI to assist in diagnosing patients. The MRI will show signs of iron accumulation in the brain (striatum, thalamus, dentate nucleus) and liver on both T1- and T2-weighted images. The images also will indicate the absence of serum ceruloplasmin, a copper-containing protein, and some combination of the following: low serum copper concentration, low serum iron concentration, high serum ferritin (a protein that enables cells to store iron) concentration, and increased iron concentration in the liver.

Age at onset is 25 to 60, and older. Psychiatric problems in patients include depression and cognitive dysfunction in individuals older than age 50.

Retinal degeneration was found in 93 percent of Japanese individuals with aceruloplasminemia [Miyajima, et. al., 2003]. Visual acuity is not affected.

Evaluations Following Initial Diagnosis

To establish the extent of disease and the individual’s needs, evaluations for the following are recommended:

  • Iron deposits. Serum ferritin concentration, brain and abdomen MRI findings, and hepatic (liver) iron and copper content by liver biopsy
  • Neurologic findings. Brain MRI and protein concentration in cerebral spinal fluid.
  • Diabetes mellitus. Blood concentrations of insulin and HbA1c, a test of blood sugar levels.
  • Retinal degeneration. Examination of the optic fundi, the interior linking of the eyeball, and fluorescein angiography, a test to examine blood vessels in the retina, choroid and iris of the eye. 
  • Medical genetics consultation

Management

Iron chelating agents, such as desferrioxamine and deferasiox, are sometimes used to decrease serum ferritin concentration, decrease brain and liver iron stores, and prevent progression of neurologic signs and symptoms in symptomatic individuals with blood hemoglobin concentration higher than 9 grams per deciliter. The chelator is combined with intravenous desferrioxamine and fresh-frozen human plasma to decrease iron content in the liver. Repetitive treatment with the plasma can improve neurologic signs and symptoms.

Also, antioxidants such as vitamin E may be used along with a chelator or oral administration of zinc to prevent tissue damage, particularly to the liver and pancreas.

Annual glucose tolerance tests starting at age 15 are recommended to evaluate for the onset of diabetes mellitus. Also, an ECC evaluation should be performed early in the course of the disease.

Avoid iron supplements.

Genetics

Aceruloplasminemia is inherited in an autosomal recessive manner. Because most of our genes exist in pairs (one coming from the mother and one coming from the father), we normally carry two working copies of each gene. When one copy of a recessive gene has a change or mutation, the person should still have normal health. That person is called a carrier.

Recessive diseases only occur when both parents are carriers for the same condition and then pass their changed genes on to their child. Statistically, there is a one in four chance that two carriers would have an affected child. The chance is one in four that their child won’t have the gene mutation.

Carrier testing for at-risk relatives and prenatal testing for pregnancies at risk are possible if both disease-causing mutations have been identified in an affected family member.

Prenatal Testing

If the disease-causing mutations have been identified in the family, prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells through amniocentesis (usually at 15 to 18 weeks’ gestation) or sampling of the chorionic villus - the finger-like projections that emerge from the outer sac surrounding the fetus - (usually at 10 to 12 weeks’ gestation).

Screening embroyos before they become implanted may be an option for some families in which the disease-causing mutations have been identified.

 

Please see the link in the right hand column on this page for more detailed information on aceruloplasminemia at Gene Reviews, which was used as a source for some of the above information.

Gene Reviews Author:

Hiroaki Miyajima, MD
First Department of Medicine
Hamamatsu University School of Medicine
Hamamatsu, Japan