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Aceruloplasminemia.

Authors

Miyajima H1.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2003 Aug 12 [updated 2015 Nov 5].

Author information

1
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

Excerpt

CLINICAL CHARACTERISTICS:

Aceruloplasminemia is characterized by iron accumulation in the brain and viscera. The clinical triad of retinal degeneration, diabetes mellitus (DM), and neurologic disease is seen in individuals ranging from age 25 years to older than 70 years. The neurologic findings of movement disorder (blepharospasm, grimacing, facial and neck dystonia, tremors, chorea) and ataxia (gait ataxia, dysarthria) correspond to regions of iron deposition in the brain. Individuals with aceruloplasminemia often present with anemia prior to onset of DM or obvious neurologic problems. Cognitive dysfunction including apathy and forgetfulness occurs in more than half of individuals with this condition.

DIAGNOSIS/TESTING:

Aceruloplasminemia, a disorder of iron metabolism caused by the complete absence of ceruloplasmin ferroxidase activity, is caused by pathogenic variants in CP, which encodes ceruloplasmin. The diagnosis of aceruloplasminemia in a symptomatic individual relies on demonstration of the absence of serum ceruloplasmin and some combination of the following: low serum copper concentration, low serum iron concentration, high serum ferritin concentration, and increased hepatic iron concentration. The diagnosis is strongly supported by characteristic MRI findings of abnormal low intensities reflecting iron accumulation in the brain (striatum, thalamus, dentate nucleus) and liver on both T1- and T2-weighted images.

MANAGEMENT:

Treatment of manifestations: Iron chelating agents (i.e., desferrioxamine or deferasirox) to decrease serum ferritin concentration, decrease brain and liver iron stores, and prevent progression of neurologic signs/symptoms in symptomatic individuals with blood hemoglobin concentration higher than 9 g/dL; combined IV desferrioxamine and fresh-frozen human plasma (FFP) is effective in decreasing iron content in the liver; repetitive FFP treatment can improve neurologic signs/symptoms; 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. Surveillance: Annual glucose tolerance test starting at age 15 years to evaluate for the onset of diabetes mellitus; ECG evaluation early in the course of the disease; evaluation of thyroid and liver function and complete blood count annually starting at the time of diagnosis. Agents/circumstances to avoid: Iron supplements. Evaluation of relatives at risk: If the pathogenic variants in the family are known, molecular genetic testing of asymptomatic sibs of a proband allows for early diagnosis and initiation of surveillance and treatment. If pathogenic variants are unknown, monitoring of serum concentrations of hemoglobin and hemoglobin A1c in asymptomatic sibs is recommended.

GENETIC COUNSELING:

Aceruloplasminemia is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the CP pathogenic variants in the family have been identified.

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