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A rare adult-onset disorder of neurodegeneration with brain iron accumulation (NBIA) characterized by anemia, retinal degeneration, diabetes and various neurological symptoms.
ORPHA:48818Classification level: Disorder
To date 56 cases have been reported and prevalence has been estimated at about 1/1,000,000-1/1,200,000.
Aceruloplasminemia presents in adulthood with neurological symptoms including ataxia, involuntary movements (blepharospasm, grimacing, facial and neck dystonia, tremors, and chorea), parkinsonism, depression, and cognitive dysfunction accompanied by retinal degeneration, diabetes mellitus, and iron-refractory anemia.
Aceruloplasminemia is caused by a complete absence of ceruloplasmin ferroxidase activity caused by homozygous mutation of the ceruloplasmin (CP) gene (3q23-q24).
Diagnosis is based on the absence of serum ceruloplasmin and some combination of low serum copper concentration, low serum iron concentration, high serum ferritin concentration as well as hepatic iron overload. The diagnosis is strongly supported by characteristic MRI findings of abnormal low intensities reflecting iron accumulation on the brain (striatum, thalamus, dentate nucleus) and liver on both T1- and T2- weighted images. Genetic testing can confirm the diagnosis.
Differential diagnoses include other forms of later-onset, slowly progressing NBIA including atypical pantothenate kinase-associated neurodegeneration (PKAN) and neuroferritinopathy, hereditary hemochromatosis, Wilson disease, Huntington disease, dentatorubral pallidoluysian atrophy (DRPLA), juvenile Parkinson disease, hereditary spinocerebellar ataxias (see these terms) and drug effects or toxicity.
Prenatal testing for pregnancies at increased risk may be available through laboratories offering custom prenatal testing if the disease-causing mutations have been identified in an affected family member.
Aceruloplasminemia is inherited in an autosomal recessive manner.
Management and treatment
Treatment is based on intravenous and oral iron chelators (deferiprone or deferasirox), which have been associated with improvement in diabetes and neurological symptoms. Combined IV desferrioxamine and fresh-frozen human plasma (FFP) is effective in decreasing iron content in the liver. Antioxidants such as vitamin E and oral administration of zinc may prevent tissue damage.
Prognosis may include heart failure due to cardiac iron overload. To date five patients with aceruloplasminemia are known to have died from heart failure probably due to cardiac iron overload in their sixties. In the absence of heart failure and with good treatment of diabetes, the prognosis is good.
Article for general public
- Clinical genetics review
- English (2018)